2013 EDITION
Mdecins Sans Frontires February 2013 All rights reserved for all countries. No reproduction, translation and adaptation may be done without the prior permission of the Copyright owner. ISBN 2-906498-86-6
Clinical guidelines
Contributors:
(S) Surgeon, (L) Laboratory technician, (MD) Medical Doctor, (N) Nurse, (AA) Anaesthetist-assistant, (Ph) Pharmacist, (P) Psychologist
P. Albajar (MD), S. Balkan (MD), P. Barel (MD), E. Baron (MD), T. Baubet (MD), M. Biot (MD), F. Boillot (S), L. Bonte (L), M.C. Bottineau (MD), M.E. Burny (N), V. Captier (N), M. Cereceda (MD), F. Charles (MD), M.J de Chazelles (MD), D. Chdorge (N), A.S. Coutin (MD), C. Danet (MD), B. Dehaye (S), K. Dilworth (MD), F. Drogoul (MD), F. Fermon (N), B. Graz (MD), B. GuyardBoileau (MD), G. Hanquet (MD), G. Harczi (N), M. van Herp (MD), C. Hook (MD), V. Ioos (MD), K. de Jong (P), S. Lagrange (MD), X. Lassalle (AA), B. Laumont (P), D. Laureillard (MD), M. Lekkerkerker (MD), J. Maritoux (Ph), J. Menschik (MD), D. Mesia (MD), A. Minetti (MD), R. Murphy (MD), N. Peyraud (MD), J. Pinel (Ph), J. Rigal (MD), K. Ritmeijer (MD), L. Shanks, (MD), M. de Smet (MD), S. Seyfert (MD), J. Stassijns (MD), F. Varaine (MD), B. Vasset (MD)
We would like to thank the following doctors for their invaluable help: O. Bouchaud, E. Bottieau, A. Briend, M. Boussinesq, F. Chappuis, J.P. Chippaux, J. Dupouy Camet, F. Delange, O. Fontaine, P.Y. Fournier, F. Van Gompel, M. Goyffon, S. Halperin, J. Janin, B. Lagardre, J.D. Law-Koune, F. Nosten, G. Potel, M. Rosenheim, J. Ross, C.E. Rupprecht, J. Sal Rach, P. Prez Simarro, M. Soriano, K. Stille, T. Vallot, P. Vigeral, M. Warrell, A.Weissman and N. White. Translated from French by K. Alberti, V. Grouzard, N. Harris and C. Lopez-Serraf Illustrations: Germain Pronne Design and layout: Evelyne Laissu
Foreword
This diagnostic and treatment manual is designed for use by medical professionals involved in curative care at the dispensary and hospital levels. We have tried to respond in the simplest and most practical way possible to the questions and problems faced by field medical staff, using the accumulated field experience of Mdecins Sans Frontires, the recommendations of reference organizations such as the World Health Organization (WHO) and specialized works in each field. This edition touches on the curative and, to a lesser extent, the preventive aspects of the main diseases encountered in the field. The list is incomplete, but covers the essential needs.
This manual is used not only in programmes supported by Mdecins Sans Frontires, but also in other programmes and in other contexts. It is notably an integral part of the WHO Emergency Health Kit. Mdecins Sans Frontires has also issued French and Spanish editions. Editions in other languages have also been produced in the field. This manual is a collaborative effort of medical professionals from many disciplines, all with field experience.
Despite all efforts, it is possible that certain errors may have been overlooked in this manual. Please inform the authors of any errors detected. It is important to remember, that if in doubt, it is the responsibility of the prescribing medical professional to ensure that the doses indicated in this manual conform to the manufacturers specifications. The authors would be grateful for any comments or criticisms to ensure that this manual continues to evolve and remains adapted to the reality of the field. Comments should be addressed to: Mdecins Sans Frontires - Guidelines 8 rue St-Sabin - 75011 Paris Tel.: +33.(0)1.40.21.29.29 Fax: +33.(0)1.48.06.68.68 e.mail: guide.clinical@msf.org
This manual is also available on the internet at www.msf.org. As treatment protocols for certain diseases are constantly changing, medical staff are encouraged to check this website for updates of this edition.
An alphabetical index at the end of the manual with the names of the diseases and symptoms.
Names of drugs
The International Non-proprietary Name (INN) of drugs is used in this manual. A list of current proprietary names can be found at the end of the manual.
Abbreviations used
kg g mg g IU M mmol ml dl = = = = = = = = = Units kilogram gram milligram microgram international unit million millimole millilitre decilitre PO IM IV SC Administration route = = = = per os = oral intramuscular intravenous subcutaneous
For certain drugs NSAID = nonsteroidal anti-inflammatory drug SMX + TMP = sulfamethoxazole + trimethoprim = cotrimoxazole
Doses of the combination sulfamethoxazole + trimethoprim (cotrimoxazole) are expressed as SMX + TMP, for example: Children: 30 mg SMX + 6 mg TMP/kg/day Adults: 1600 mg SMX + 320 mg TMP/day Doses of the combination amoxicillin + clavulanic acid (co-amoxiclav) are expressed in amoxicillin. Doses of certain antimalarial drugs are expressed in base (and not in salts). Doses of iron are expressed in elemental iron (and not in ferrous salts).
Expression of doses
Table of contents
Introduction page 8 page 15
Shock (17) Seizures (23) Fever (26) Pain (29) Anaemia (37) Severe acute malnutrition (40) Rhinitis and rhinopharyngitis [common cold] (49) Acute sinusitis (50) Acute laryngitis (51) Acute pharyngitis (53) Diphtheria (55) Otitis (57) Whooping cough [pertussis] (60) Bronchitis (62) Bronchiolitis (64) Acute pneumonia (66) Staphylococcal pneumonia (73) Asthma (74) Pulmonary tuberculosis (79) Gastrointestinal disorders Respiratory diseases
page 47
Acute diarrhoea (83) Shigellosis (86) Amoebiasis (88) Disorders of the stomach and duodenum (89) Stomatitis (92)
page 81
Skin diseases
Dermatology (97) Scabies (98) Lice [pediculosis] (101) Superficial fungal infections (103) Bacterial skin infections (105) Cutaneous anthrax (109) Treponematoses (111) Leprosy (113) Herpes simplex and herpes zoster (116) Other skin disorders (117) Eye diseases
page 95
Xerophthalmia [vitamin A deficiency] (121) Conjunctivitis (123) Trachoma (126) Other pathologies: onchocerciasis, loiasis, pterygium, cataract (128)
page 119
Parasitic diseases
Protozoan infections: Malaria (131) Human african trypanosomiasis (139) American trypanosomiasis (142) Leishmaniases (144) Intestinal protozoan infections [parasitic diarrhoea] (147) Helminthic infections: Flukes (149) Schistosomiasis (150) Cestodes (152) Nematode infections (154) Filariasis (157)
page 129
Bacterial diseases
Bacterial meningitis (165) Tetanus (170) Typhoid fever (174) Brucellosis (176) Plague (178) Leptospirosis (180) Relapsing fever [borreliosis] (182) Eruptive rickettsioses (185)
page 163
Viral diseases
Measles (189) Poliomyelitis (192) Rabies (194) Viral hepatitis (198) Dengue fever (201) Viral haemorrhagic fevers (204) HIV infection and AIDS (207) Genito-urinary diseases
page 187
Uro-nephrologic diseases: Urolithiasis (223) Acute cystitis (224) Acute pyelonephritis (226) Acute prostatitis (228) Genital infections (GI) (229): Urethral discharge (231) Abnormal vaginal discharge (233) Genital ulcers (236) Lower abdominal pain in women (239) Upper genital tract infections (240) Veneral warts (243) Major genital infections summary (244) Metrorrhagia (246) Medical and minor surgical procedures Dressings (253) Treatment of a simple wound (256) Burns (266) Abscesses (274) Pyomyositis (279) Leg ulcers (281) Venomous bites and stings (283) Dental infections (287) Mental/psychical disorders in adults Anxiety (291) Insomnia (292) Agitation (293) Mental confusion (294) Post-traumatic stress disorder (295) Depression (297) Psychotic disorders (300) Other conditions Hypertension (305) Heart failure in adults (309) Endemic goitre and iodine deficiency (312) Annexes
page 221
10
page 251
11
page 289
12
page 303
The interagency emergency health kit/Annex 2 - WHO (315) Practical advice for writing medical certificates in the event of sexual violence (322) List of the drugs mentioned in this guide, including the INN as well as the most common synonyms and proprietary names (325) Main references Index
page 313
Introduction
Introduction
Curative care is one component of health programmes. It is important to remember that the other components also need to be developed. These components include programmes focusing on: palliative care (including pain control), psychological support, prevention (including the Expanded Programme of Immunization (EPI), maternal-child health etc.), nutrition, water, hygiene and sanitation.
At an individual level: to cure the patient of disease and to minimize or prevent the consequences for the individual and those in close contact (i.e. preventing transmission when possible). At a population level: to reduce the mortality and the consequences of morbidity of the most prevalent and important diseases in the population. For certain endemic diseases (tuberculosis, leprosy, trypanosomiasis etc.): curative care can reduce transmission if a large enough proportion of the population is treated. Often, this objective is only achieved through specific control programmes which are not extensively discussed in this manual. When defining a strategy for a medical intervention, medical decision makers must take into account the priority diseases: those with the highest frequency and mortality. Priority diseases vary with context (conflict, natural disasters, etc.) and geographical region. Nevertheless, there is a relatively standard epidemiological profile with quantitative variations. An initial assessment, both qualitative (disease distribution) and if possible quantitative (mortality, incidence, prevalence and case fatality), is still necessary. This evaluation identifies the most common diseases (diarrhoea, measles, acute respiratory tract infections, malaria, wounds etc.) and the population groups exposed and at risk (children under 5 years, pregnant women). These diseases and populations constitute the priority targets of a programme. For rehabilitation programmes and programmes to support pre-existing health structures, detailed information is sometimes available from the health structures or from the Ministry of Health. The evaluation consists of assessing the information available and filling in any missing data. In very isolated contexts or when there is population displacement, no information is available and it is always necessary to do a complete assessment. Once the priority diseases are identified and health policy, means and resources (list of essential drugs, Ministry of Health protocols, staff and level of training, health services, functioning programmes etc.) are known, programmes can be defined and initiated. This manual and the manual, Essential drugs practical guidelines, are tools to help in the definition and implementation (protocols, training, retraining) of curative programmes.
8
II - Strategy
Introduction
The training and competence level of medical staff (medical auxilaries, medical assistants, nurses, midwives, doctors etc.) vary by country and health structure (health post, dispensary, health centre, hospital). Evaluation should identify their technical level while recognising that in some situations, the staff have not always received prior training.
Drugs
Selection of drugs depends on the priorities and needs, but also on other criteria: effectiveness, local resistance, adverse effects administration route, length of treatment, number of doses per day, expected compliance stability, availability, price The WHO Essential Medicines List is the basic framework, but the choice of drugs has to be adapted to the epidemiological profile, the competence of the staff and the possibility (or lack thereof) to refer very sick patients. Certain drugs proposed in this manual are not included in the WHO Essential Medicines List.
Treatment protocols
Standard protocols improve diffusion and use of effective treatment. They should: give precise instructions (INN of the medication, indications, dosage, route of administration, length of treatment, contra-indications, adverse effects, precautions); favour the most effective drug with the least adverse effects; be supported by clinical, epidemiological and scientific data and be discussed and agreed upon by the users; be practical, simple, understandable and adapted to the field; facilitate the training and retraining of medical staff; facilitate the organization of health services (e.g. management, pharmacy); be evaluated.
The treatment protocols include drug prescription, as well as other measures (curative and preventive), indications for referral to a higher level of care and an indication of which diseases must be reported (cholera, measles etc.).
Formulation depends on the training of the prescribing medical staff: doctors are trained in terms of diseases (pneumonia, malaria etc.) while medical auxilaries use a symptomatic approach (cough and difficulty in breathing, fever and chills etc.).
9
Introduction
Protocols must take into account the cultural context (e.g. to discourage covering a febrile child if that is the cultural practise) and the environment (avoid the classic mistakes, e.g. recommending that water be boiled when fuel or firewood is scarce). The protocols must take into account drug supply (what is the availability?) and presentation (e.g. are the antimalarials labelled in salts or base?). Protocols must facilitate compliance. Short treatments with few doses are recommended. Single dose treatment, when indicated, is the best choice. The number of different drugs prescribed must also be limited whenever possible. For similar effectiveness oral or rectal drugs are preferred over injections in order to reduce complications, cost, risk of transmission of hepatitis B, HIV etc.
Diagnostic methods
The methods used depend on the services available and the technical level of the staff. They have a direct influence on the establishment of protocols and the content of the drug list. Usually diagnosis is made on a basis of history taking, clinical examination and basic laboratory tests (as defined by the WHO). A - History taking A medical consultation is a special occasion to listen to the patient and to ask relevant questions to determine the cause of the complaint. During the interview, the history of the current illness, the signs and symptoms, prior illness and any treatment already received are specified. Only by listening attentively is it possible to put the patients complaint in a larger context of suffering. For example, during a consultation, physical violence, sexual violence or abuse may come to light, while this type of complaint is rarely expressed spontaneously by the victim. It is the clinicians responsibility to take a global view of the situation that includes: psychological, legal (completing a medical certificate) and social aspects and direct clinical care. B - Clinical examination Clinical examination is essential: the diagnosis and treatment depend directly on its quality. It is important to know or to learn a technique of clinical assessment that is both complete and rapid, keeping in mind the need for quality and efficiency. A technique, or a strategy, is even more important in field conditions as the number of patients often stretches the medical possibilities and apart from basic laboratory examinations, the complementary examinations are often nonexistent. The following examination framework is an example that should be adapted to each case. It emphasises the advantages of a systematic approach. Context of the examination Routine examination: e.g. prenatal consultation or Mother and Child Health (MCH). The emphasis of the examination is predefined by the programme objectives (nutritional state, anaemia, prevention of tetanus etc.). As a result of a complaint: the usual situation at a dispensary. The most common complaints are fever, pain, diarrhoea and cough.
10
Introduction
A few rules A systematic approach reduces omissions and saves time. An interpreter may be needed; however, translation does not always accurately reflect the complaints of the patient. Learning the names of the main clinical signs and common diseases in the local language helps overcome this problem. The choice of an interpreter must take into consideration the sex (e.g. a female for gynaecology and obstetrics) and the acceptability by the patient (respecting confidentiality). The examination Physical examination: the patient should be undressed if possible. first look at the general condition of the patient in order to judge the severity of illness: nutritional status (weight and, in children, height), hydration, anaemia, temperature. examine each system: use a systematic approach starting with the system related to the patients complaint. Laboratory examinations: if necessary and if available Imaging techniques: x-ray and ultrasonography, if necessary and if available C - Role of the laboratory
A basic medical laboratory can play an important and irreplaceable role. However, technical constraints (the need for a trained and competent technician), logistical constraints (regular supply of material, reagents, electricity), time constraints (each examination takes a minimum time) and quality constraints (which depends on all the points just mentioned) should not be underestimated. Two levels of examinations can be defined: Basic examination
Blood Haematology haemoglobin (Lovibond) WBC and differentials Transfusion blood group + rhesus HIV, hepatitis B and C, syphilis RPR Thick and thin films malaria, some filariases, trypanosomiasis, visceral leishmaniasis, borreliosis Rapid tests malaria HIV, hepatitis B and C etc. Kochs bacillus reagent strip test (glucose, protein)
gonococcus, trichomonas
look for and identify pathogens (including rapid test for meningitis) cell count and protein (Pandy test)
11
Introduction
More specific examinations are defined in relation to the programme. A laboratory can be used in three complementary ways: Clinically: examinations are requested for individuals depending on the clinical picture. The aim is to orient a diagnosis (e.g. leucocytosis in a full blood count) or to determine or eliminate an aetiology (e.g. stool examination for parasites, blood smear, rapid test).
Epidemiologically: the objective is to facilitate diagnosis and treatment. By studying a sample of patients presenting with similar clinical profiles an aetiology can be specified. The validity (sensitivity and specificity) of the particular symptoms or syndrome can also be studied. Through these means appropriate treatment protocols can be introduced for all patients presenting with the same symptoms or syndrome. For example: is the syndrome non-febrile bloody diarrhoea predictive of amoebic dysentery? An investigation of approximately 100 patients will answer this question. If a significant proportion of the samples are positive, an appropriate treatment can be given to all patients presenting with this syndrome. This approach, while practical during some epidemics, should not stop the practitioner from considering differential diagnosis as the sensitivity of a syndrome is rarely 100% The combination of clinical examination and complementary examinations should result in an aetiological diagnosis if possible, if not, a symptomatic or syndromic diagnosis. Operational research: laboratory examinations are also used during resistance studies (malaria) and for other operational research.
Treatment
Prescribe a treatment: aetiological (treat the cause) symptomatic give relevant advice, whether or not the patient was treated or refer.
Record the essential information in a register and on an individual patient record (see the example of a health card, annex 3), an examination card or in a family health booklet. Information should include: diagnosis is important positive and negative signs (e.g. bloody diarrhoea without fever) laboratory examinations requested and the results drugs prescribed (in INN), dosage, duration
Training
Training and retraining of staff should be carried out according to their technical level (this should be evaluated) and is therefore context dependent. This manual and other documents may be useful tools in defining and meeting training objectives.
12
Introduction
For many reasons (lack of information, different cultural perceptions), a significant proportion of seriously ill, but curable patients may not present at health centres for treatment, or may present only when they are in the advanced stages of disease. Public awareness and dissemination of information at all levels, along with the quality of services, contribute to increase the proportion of the population receiving appropriate care.
V - Programme evaluation
Functioning
Assessment of activities, trends in case fatality rates, respect of protocols, management of the pharmacy, drug consumption, quality of prescriptions, orders, reports, the register etc. This information helps in programme management (orders, staffing). The morbidity data collected at the dispensary level and their analysis contribute to epidemiological surveillance. Trends of priority diseases by person, time and place can be monitored (see Epidemiological reports, annex 2) and an early warning systems can be put in place.
Coverage of need
This depends on the accessibility and on the populations perception of the health care system. The goal is to determine the proportion of sick people who are actually being treated. The evaluation is feasible by surveying representative samples of the population (see below).
The evaluation is complex. It refers to the objectives of reducing mortality, morbidity, etc. Survey protocols exist but are very difficult to put into practice (large sample size) and the surveys must be repeated to show trends.
13
CHAPTER 1
Shock
Acute circulatory failure leading to inadequate tissue perfusion which, if prolonged, results in irreversible organ failure. Mortality is high without early diagnosis and treatment.
Relative hypovolaemia due to vasodilation without concomitant increase in intravascular volume: Anaphylactic reaction: allergic reaction to insect bites or stings; drugs, mainly neuromuscular blockers, antibiotics, acetylsalicylic acid, colloid solutions (dextran, modified gelatin fluid); equine sera; vaccines containing egg protein; food, etc. Acute haemolysis: severe malaria, drug poisoning (rare).
Septic shock
By a complex mechanism, often including vasodilation, heart failure and absolute hypovolaemia.
Cardiogenic shock
By decrease of cardiac output: Direct injury to the myocardium: infarction, contusion, trauma, poisoning. Indirect mechanism: arrhythmia, constrictive pericarditis, haemopericardium, pulmonary embolism, tension pneumothorax, valvular disease, severe anaemia, beri beri, etc.
Shock
Septic shock High fever or hypothermia (< 36C), rigors, confusion BP may be initially maintained, but rapidly, same pattern as for hypovolaemic shock.
Cardiogenic shock Respiratory signs of left ventricular failure (acute pulmonary oedema) are dominant: tachypnoea, crepitations on auscultation. Signs of right ventricular failure: raised jugular venous pressure, hepatojugular reflux, sometimes alone, more often associated with signs of left ventricular failure.
The aetiological diagnosis is oriented by: The context: trauma, insect bite, ongoing medical treatment, etc. The clinical examination: fever skin pinch consistent with dehydration thoracic pain from a myocardial infarction or pulmonary embolus abdominal pain or rigidity of the abdominal wall from peritonitis, abdominal distension from intestinal obstruction blood in stools, vomiting blood in intestinal haemorrhage subcutaneous crepitations, likely anaerobic infection
Management
In all cases
Emergency: immediate attention to the patient. Warm the patient, lay him flat, elevate legs (except in respiratory distress, acute pulmonary oedema). Insert a peripheral IV line using a large calibre catheter (16G in adults). If no IV access, use intraosseous route. Oxygen therapy, assisted ventilation in the event of respiratory distress. Assisted ventilation and external cardiac compression in the event of cardiac arrest. Intensive monitoring: consciousness, pulse, BP, CRT, respiratory rate, hourly urinary output (insert a urinary catheter) and skin mottling.
18
Priority: restore vascular volume as quickly as possible: Insert 2 peripheral IV lines (catheters 16G in adults) Ringer Lactate or 0.9% sodium chloride: replace 3 times the estimated losses and/or plasma substitute: replace 1.5 times the estimated losses
Transfuse: classically once estimated blood loss represents approximately 30 to 40% of blood volume (25% in children). The blood must be tested (HIV, hepatitis B and C, syphilis, etc.) Refer to the MSF handbook, Blood transfusion. Severe acute dehydration due to bacterial/viral gastroenteritis Urgently restore circulating volume using IV bolus therapy: Ringer Lactate or 0.9% sodium chloride: Children < 2 months: 10 ml/kg over 15 minutes. Repeat (up to 3 times) if signs of shock persist. Children 2-59 months: 20 ml/kg over 15 minutes. Repeat (up to 3 times) if signs of shock persist. Children 5 years and adults: 30 mg/kg over 30 minutes. Repeat once if signs of shock persist. Closely monitor the patient; be careful to avoid fluid overload in young children and elderly patients).
Then, replace the remaining volume deficit using continuous infusion until signs of dehydration resolve (typically 70 ml/kg over 3 hours). Note: in severely malnourished children the IV rate is different than those for healthy children (see Severe acute malnutrition, page 40). Severe anaphylactic reaction Determine the causal agent and remove it, e.g. stop ongoing injections or infusions, but if in place, maintain the IV line. Administer epinephrine (adrenaline) IM, into the antero-lateral tight, in the event of hypotension, pharyngolaryngeal oedema, or breathing difficulties: Use undiluted solution (1:1000 = 1 mg/ml) and a 1 ml syringe graduated in 0.01 ml: Children under 6 years: 0.15 ml Children from 6 to 12 years: 0.3 ml Children over 12 years and adults: 0.5 ml In children, if 1 ml syringe is not available, use a diluted solution, i.e. add 1 mg epinephrine to 9 ml of 0.9% sodium chloride to obtain a 0.1 mg/ml solution (1:10 000): Children under 6 years: 1.5 ml Children from 6 to 12 years: 3 ml
19
Shock
At the same time, administer rapidly Ringer lactate or 0.9% sodium chloride: 1 litre in adults (maximum rate); 20 ml/kg in children, to be repeated if necessary. If there is no clinical improvement, repeat IM epinephrine every 5 to 15 minutes.
In patients with bronchospasm, epinephrine is usually effective. If the spasm persists give 10 puffs of inhaled salbutamol. Septic shock Vascular fluid replacement with Ringer Lactate or 0.9 % sodium chloride or plasma substitute.
Corticosteroids have no effect in the acute phase. However, they must be given once the patient is stabilized to prevent recurrence in the short term: hydrocortisone hemisuccinate IV or IM Children: 1 to 5 mg/kg/24 hours in 2 or 3 injections Adults: 200 mg every 4 hours
In shock persists after 3 IM injections, administration of IV epinephrine at a constant rate by a syringe pump is necessary: Use a diluted solution, i.e. add 1 mg epinephrine (1:1000) to 9 ml of 0.9% sodium chloride to obtain a 0.1 mg/ml solution (1:10 000): Children: 0.1 to 1 microgram/kg/minute Adults: 0.05 to 0.5 microgram/kg/minute If syringe pump is not available, see box page 22.
Use of vasoconstrictors: dopamine IV at a constant rate by syringe pump (see box page 22): 10 to 20 micrograms/kg/minute or, if not available epinephrine IV at a constant rate by syringe pump: Use a diluted solution, i.e. add 1 mg epinephrine (1:1000) to 9 ml of 0.9% sodium chloride to obtain a 0.1 mg/ml solution (1:10 000). Start with 0.1 microgram/kg/minute. Increase the dose progressively until a clinical improvement is seen. If syringe pump is not available, see box page 22.
Look for the origin of the infection (abscess; ENT, pulmonary, digestive, gynaecological or urological infection etc.). Antibiotic therapy according to the origin of infection:
Cutaneous staphylococci, streptococci Origin Antibiotic therapy Alternative cloxacillin + gentamicin
Pulmonary pneumococci, Haemophilus influenzae Intestinal or biliary enterobacteria, anaerobic bacteria, enterococci Gynaecological streptococci, gonococci, anaerobic bacteria, E. coli Other or undetermined 20
1. A few symptomes and syndromes ampicillin IV Children and adults: 150 to 200 mg/kg/day in 3 injections (every 8 hours) cloxacillin IV
Children: 100 to 200 mg/kg/day in 4 divided doses (every 6 hours) Adults: 8 to 12 g/day in 4 divided doses (every 6 hours)
co-amoxiclav (amoxicillin/clavulanic acid) ceftriaxone slow
IV1 Children: 100 mg/kg as a single injection on the first day, then 50 mg/kg once daily Adults: 2 g once daily
ciprofloxacin PO gentamicin IM Children and adults: 3 to 6 mg/kg once daily or in 2 divided doses metronidazole IV
slow IV Children: 75 to 150 mg/kg/day in 3 divided doses (every 8 hours) Adults: 3 to 6 g/day in 3 divided doses (every 8 hours)
(by nasogastric tube) Children: 15 to 30 mg/kg/day in 2 divided doses Adults: 1.5 g/day in 2 divided doses
Corticosteroids: not recommended, the adverse effects outweigh the benefits Cardiogenic shock The objective is to restore efficient cardiac output. The treatment of cardiogenic shock depends on its mechanism. Acute left heart failure with pulmonary oedema Acute pulmonary oedema (see Heart failure in adults, page 309). In the event of worsening signs with vascular collapse, use a strong inotrope: dopamine IIV at a constant rate by syringe pump (see box page 22): 3 to 10 micrograms/kg/minute
Children: 20 to 30 mg/kg/day in 3 divided doses (every 8 hours) Adults: 1 to 1.5 g/day in 3 divided doses (every 8 hours)
Once the haemodynamic situation allows (normal BP, reduction in the signs of peripheral circulatory failure), nitrates or morphine may be cautiously introduced.
Digoxin should no longer be used for cardiogenic shock, except in the rare cases when a supraventricular tachycardia has been diagnosed by ECG. Correct hypoxia before using digoxin. digoxin slow IV Children: one injection of 0.010 mg/kg (10 micrograms/kg), to be repeated up to 4 times/24 hours if necessary Adults: one injection of 0.25 to 0.5 mg, then 0.25 mg 3 or 4 times/24 hours if necessary
1 The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must
never be administered by IV route. For IV administration, water for injection must always be used.
21
Shock
Cardiac tamponade: restricted cardiac filling as a result of haemopericardium or pericarditis. Requires immediate pericardial tap after restoration of circulating volume. Tension pneumothorax: drainage of the pneumothorax. Symptomatic pulmonary embolism: treat with an anticoagulant in a hospital setting.
Administration of dopamine or epinephrine at a constant rate requires the following conditions: close medical supervision in a hospital setting; use of a dedicated vein (no other infusion/injection in this vein), avoid the antecubital fossa if possible; use of an electric syringe pump (or infusion pump); progressive increase and adaptation of doses according to clinical response; intensive monitoring of drug administration, particularly during syringe changes. Example:
dopamine:
10 micrograms/kg/minute in a patient weighing 60 kg Hourly dose: 10 (micrograms) x 60 (kg) x 60 (min) = 36 000 micrograms/hour = 36 mg/hour In a 50 ml syringe, dilute one 200 mg-ampoule of dopamine with 0.9% sodium chloride to obtain 50 ml of solution containing 4 mg of dopamine per ml. For a dose of 36 mg/hour, administer the solution (4 mg/ml) at 9 ml/hour.
Example for epinephrine: In adults: Dilute 10 ampoules of 1 mg epinephrine (10 000 micrograms) in 1 litre of 5% glucose or 0.9% sodium chloride to obtain a solution containing 10 micrograms of epinephrine per ml. Knowing that 1 ml = 20 drops, in an adult weighting 50 kg: 0.1 microgram/kg/minute = 5 micrograms/minute = 10 drops/minute 1 microgram/kg/minute = 50 micrograms/minute = 100 drops/minute, etc. In children: Dilute 1 ampoule of 1 mg epinephrine (1000 micrograms) in 100 ml of 5% glucose or 0.9% sodium chloride to obtain a solution containing 10 micrograms of epinephrine per ml. For administration, use a paediatric infusion set; knowing that 1 ml = 60 drops, in a child weighting 10 kg: 0.1 microgram/kg/minute = 1 microgram/minute = 6 drops/minute 0.2 microgram/kg/minute = 2 micrograms/minute = 12 drops/minute, etc.
If there is no electric syringe pump , dilution in an infusion bag may be considered. However, it is important to consider the risks related to this type of administration (accidental bolus or insufficient dose). The infusion must be constantly monitored to prevent any, even small, change from the prescribed rate of administration.
Note: account for all infused volumes when recording ins and outs.
22
Seizures
Involuntary movements of cerebral origin (stiffness followed by clonic movements), accompanied by a loss of consciousness, and often urinary incontinence (generalized tonic-clonic seizures). It is important to distinguish seizures from pseudo-seizures (e.g. in hysteria or tetany) during which consciousness may appear altered but is not lost. 2 priorities: stop the seizures and determine the cause. In pregnant women, eclamptic seizures require specific medical and obstetrical care (see page 25).
Protect from trauma, maintain airway, place patient in recovery position, loosen clothing. Most seizures are quickly self-limited. Immediate administration of an anticonvulsant is not systematic. If generalized seizure lasts more than 3 minutes, use diazepam to stop it: Children: 0.5 mg/kg preferably rectally1 without exceeding 10 mg. IV administration is possible (0.3 mg/kg over 2 or 3 minutes), only if means of ventilation are available (Ambu bag and mask). Adults: 10 mg rectally or slowly IV. In all cases: Dilute 10 mg (2 ml) of diazepam in 8 ml of 5% glucose or 0.9% sodium chloride. If convulsion continues, repeat dose once after 5 minutes. In infants and elderly patients, monitor respiration and blood pressure. If convulsion continues after the second dose, treat as status epilepticus.
diazepam
Look for the cause of the seizure and evaluate the risk of recurrence. Keep diazepam and glucose available in case the patient starts seizing again. Several distinct seizures without complete restoration of consciousness in between or an uninterrupted seizure lasting more than 10 minutes. Protect from trauma, loosen clothing, maintain airway and administer oxygen as required. Insert an IV line. Administer by slow IV (over 5 minutes): 5 ml/kg of 10% glucose in children and 1 ml/kg of 50% glucose in adults. If diazepam (see above) has not stopped the seizure, continue with phenobarbital by IV infusion: Children under 12 years: 20 mg/kg (maximum 1 g) in 100 ml of 0.9% sodium chloride or 5% glucose administered over 20 minutes minimum (never exceed 1 mg/kg/minute). If necessary, a second dose of 10 mg/kg may be administered (as above) 15 to 30 minutes after the first dose. Children over 12 years and adults: 10 mg/kg (max. 1 g) in 100 ml of 0.9% sodium chloride or 5% glucose administered over 20 minutes minimum (never exceed 1 mg/kg/minute). If necessary, a second dose of 5 to 10 mg/kg may be administered (as above) 15 to 30 minutes after the first dose.
1 For rectal administration, use a syringe without a needle, or better, cut a nasogastric tube, CH8, to a length of
23
Seizures
There is a high risk of respiratory depression and hypotension, especially in children and elderly patients. Never administer phenobarbital by rapid IV injection. Monitor closely respiration and blood pressure. Ensure that respiratory support (Ambu bag via face mask or intubation) and IV solutions for fluid replacement are ready at hand.
Further treatment
Infectious causes Severe malaria (page 131), meningitis (page 165), meningo-encephalitis, cerebral toxoplasmosis (pages 217 and 218), cysticercosis (page 153), etc. Metabolic causes Hypoglycaemia: administer glucose by slow IV injection (for administration, see page 23) to all patients who do not regain consciousness, to patients with severe malaria and to newborns and malnourished children. When possible, confirm hypoglycaemia (reagent strip test).
Febrile seizures Determine the cause of the fever. Give paracetamol (see Fever, page 26), undress the patient, wrap in damp cloth. In children under 3 years, there is usually no risk of later complications after simple febrile seizures and no treatment is required after the crisis. For further febrile episodes, give paracetamol PO.
Iatrogenic causes Withdrawal of antiepileptic therapy in a patient being treated for epilepsy should be managed over a period of 4-6 months with progressive reduction of the doses. An abrupt stop of treatment may provoke severe recurrent seizures.
Epilepsy A first brief seizure does not need further protective treatment. Only patients with chronic repetitive seizures require further regular protective treatment with an antiepileptic drug, usually over several years. Once a diagnosis is made, abstention from treatment may be recommended due to the risks associated with treatment. However, these risks must be balanced with the risks of aggravation of the epilepsy, ensuing seizure-induced cerebral damage and other injury if the patient is not treated. It is always preferable to start with monotherapy. The effective dose must be reached progressively and symptoms and drug tolerance evaluated every 15 to 20 days. An abrupt interruption of treatment may provoke status epilepticus. The rate of dose reduction varies according to the length of treatment; the longer the treatment period, the longer the reduction period (see iatrogenic causes, above). In the same way, a change from one antiepileptic drug to another must be made progressively with an overlap period of a few weeks. First line treatments for generalised tonic-clonic seizures in children under 2 years are carbamazepine or phenobarbital, in older children and adults sodium valproate or carbamazepine. For information: carbamazepine PO Children: initial dose of 2 mg/kg/day in 1 or 2 divided doses; increase every week until the optimal dose for the individual has been reached (usually 10 to 20 mg/kg/day in 2 to 4 divided doses). Adults: initial dose of 200 mg/day in 1 or 2 divided doses; increase by 200 mg every week until the optimal dose for the individual has been reached (usually 800 to 1200 mg/day in 2 to 4 divided doses).
24
Children over 20 kg: initial dose of 400 mg in 2 divided doses irrespective of weight; if necessary, increase the dose progressively until the optimal dose for the individual has been reached (usually 20 to 30 mg/kg/day in 2 divided doses). Adults: initial dose of 600 mg/day in 2 divided doses; increase by 200 mg/day every 3 days until the optimal dose for the individual has been reached (usually 1 to 2 g/day in 2 divided doses). phenobarbital PO Children: initial dose of 3 to 4 mg/kg/day at night, increase the dose progressively to 8 mg/kg/day if necessary Adults: initial dose of 2 mg/kg/day at night (without exceeding 100 mg per day), increase the dose progressively to 6 mg/kg/day if necessary
Eclampsia: seizures during the third trimester of pregnancy, most commonly in the context of pre-eclampsia (hypertension, oedema and proteinuria on reagent-strip test). Symptomatic treatment of eclampsia: Treatment of choice is magnesium sulfate by IV infusion: 4 g diluted in 0.9% sodium chloride to be administered over 15 minutes. Then infuse 1 g/hour, continue magnesium sulfate for 24 hours following delivery or the last seizure. If seizure recurs, give another 2 g by slow IV injection (over 15 minutes). Monitor urine output. Stop the treatment if urinary output is less than 30 ml/hour or 100 ml/4 hours. Before each injection, verify the concentration written on the ampoules: there is a risk of potentially fatal overdose. Always have calcium gluconate ready to reverse the effects of magnesium sulphate in the event of toxicity. Monitor patellar tendon reflex every 15 minutes during the infusion. If the patient has malaise, drowsiness, difficulty speaking or loss of patellar reflex: stop the magnesium sulfate and inject 1 g of calcium gluconate by slow, direct IV injection (over 5 to 10 minutes). Only in the absence of magnesium sulfate, use diazepam: 10 mg slow IV followed by 40 mg in 500 ml 5% glucose as a continuous infusion over 24 hours. If there is no venous access for the loading dose, give 20 mg rectally. In the event of treatment failure after 10 minutes, give a second dose of 10 mg. For direct IV or rectal administration dilute diazepam in 5% glucose or 0.9% sodium chloride to make a total volume of 10 ml. Oxygen: 4 to 6 litres/minute Nursing, hydration Urgent delivery within 12 hours Treatment of hypertension: see Hypertension, page 291 Other causes : during pregnancy, consider that seizures may also be caused by cerebral malaria or meningitis (the incidence of these diseases is increased in pregnant women, see Malaria, page 131 and Bacterial meningitis, page 165).
25
Fever
Fever
Fever is defined as a temperature higher than 37.5C axillary and 38C if measured rectally. It is accepted that axillary temperature underestimates the core body temperature by 0.5C, but this is very approximate. Use an electronic thermometer when available1. Fever is often linked, but not exclusively, with infection. All clinical examinations should include checking for fever. In a febrile patient, first look for signs of serious illness, then try to establish a diagnosis.
Signs of sepsis with signs of shock: circulatory failure, respiratory distress, purpura, confusion, coma. Signs of a systemic illness: meningeal syndrome, seizures, heart murmur on auscultation, abdominal pain, rash, etc. Patients underlying condition: malnutrition, immune suppression, splenectomy, chronic disease, the very young and the very old, bedridden patients.
Aetiology
Many different diseases, infectious or noninfectious, acute or chronic, benign or malignant, may be accompanied by fever. Among the infectious diseases requiring immediate treatment, look for: purpura fulminans bacterial meningitis severe malaria severe bacterial skin infections acute pyelonephritis with urinary retention peritonitis or gastrointestinal infection pneumonia with signs of respiratory distress subglottic or epiglottic laryngitis endocarditis septicaemia In the absence of signs of serious illness and obvious diagnosis, patients may return home with an antipyretic and should be educated to prevent dehydration (plenty of fluids) and to recognize symptoms that need medical attention. Patients should return for a new consultation if there is no improvement within 48 hours of the initial consultation or before if their condition deteriorates. In case of doubt (e.g. about the evolution, the quality of surveillance) and depending on the context (geographical distance, problems of transport), it may be better to keep patients 12 to 24 hours for observation.
Complications
Convulsions Dehydration Confusion, delirium Schock It is important, particularly in children, to look for signs of these complications, to treat them, and most importantly to prevent them.
1 Temperature should be measured over a period of 5 minutes when using a mercury thermometer.
26
Symptomatic treatment
Undress the patient. Antipyretics: paracetamol PO Children: 60 mg/kg/day in 3 or 4 divided doses Adults: 3 to 4 g/day in 3 or 4 divided doses or acetylsalicylic acid (A.A.S) PO (to be avoided in children under 16 years) Adults: 1 to 3 g/day in 3 or 4 divided doses or ibuprofen PO Children over 3 months: 30 mg/kg/day in 3 divided doses Adults: 1200 to 1800 mg/day in 3 to 4 divided doses Age Weight
Paracetamol
2 months 4 kg
1 year 8 kg
5 years 15 kg
15 years 35 kg
adult
500 mg tablet
A.A.S.
100 mg tablet
1/2
2 ml x 3
tab x 3
3 to 6 ml x 3 x3
11/2 to 3 tab x3 x3
x3
Avoid
Age
Weight
Ibuprofen
3 months 5 kg
6 years 20 kg
15 years 35 kg
adult
200 mg tablet
Do not administer
Use the graduated pipette (in kg): one pipette filled up to the graduation corresponding to the child's weight x 3
1 to 2 tab x 3
1 tab x 3 2 tab x 3
400 mg tablet
27
Fever
Continue to feed, even if a child has little appetite. The mother must be persuaded of the importance of feeding/breastfeeding. In the event of a febrile seizure: see page 24. Treatment of the cause: according to the aetiology of the fever.
Notes: Paracetamol is the drug of choice for pregnant and breast-feeding women. Acetylsalicylic acid is not recommended during the first 5 months of pregnancy, contra-indicated from the beginning of the 6 th month, and to be avoided in breastfeeding-women. Ibuprofen is not recommended during the first 5 months of pregnancy and contraindicated from the beginning of the 6th month. It can be administered to breastfeeding women as short-term treatment.
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Pain
Pain results from a variety of pathological processes. It is expressed differently by each patient depending on cultural background, age, etc. It is a highly subjective experience meaning that only the individual is able to assess his/her level of pain. Regular assessment of the intensity of pain is indispensable in establishing effective treatment.
Clinical features
Pain assessment Intensity: use a simple verbal scale in children over 5 years and adults, and NFCS or FLACC scales in children less than 5 years (see pain rating scales on following page). Pattern: sudden, intermittent, chronic; at rest, at night, on movement, during care procedures, etc. Character: burning, cramping, spasmodic, radiating, etc. Aggravating or relieving factors, etc. Of the organ or area where the pain is located. Specific signs of underlying disease (e.g. bone or osteoarticular pain may be caused by a vitamin C deficiency) and review of all systems. Associated signs (fever, weight loss, etc.) The synthesis of information gathered during history taking and clinical examination allows aetiological diagnosis and orients treatment. It is important to distinguish: Nociceptive pain: it presents most often as acute pain and the cause-effect relationship is usually obvious (e.g. acute post-operative pain, burns, trauma, renal colic, etc.). The pain may be present in different forms, but neurological exam is normal. Treatment is relatively well standardized.
Clinical examination
Synthesis
Neuropathic pain, due to a nerve lesion (section, stretching, ischaemia): most often chronic pain. On a background of constant, more or less localized pain, such as paraesthesia or burning, there are recurrent acute attacks such as electric shock-like pain, frequently associated with disordered sensation (anaesthesia, hypo or hyperaesthesia). This type of pain is linked to viral infections directly affecting the CNS (herpes simplex, herpes zoster), neural compression by tumors, postamputation pain, paraplegia, etc. Mixed pain (cancer, HIV) for which management requires a broader approach.
29
Pain
Scoring
Moderate pain 2 ++
Write down
No particular expression Occasional grimace or or smile frown, withdrawn, disinterested Normal position or relaxed Lying quietly, normal position, moves easily Uneasy, restless, tense Squirming, shifting back and forth, tense Reassured by occasional touching, hugging or being talked to, distractible
Each category is scored from 0 to 2, giving a final score between 0 and 10. 0 to 3: mild pain, 4 to 7: moderate pain, 7 to 10: severe pain Observational evaluation scale - Children under 2 months
Scoring Brow bulge
no no no no
Open lips
Treatment
Treatment depends on the type and intensity of the pain. It may be both aetiological and symptomatic if a treatable cause is identified. Treatment is symptomatic only in other cases (no cause found, non-curable disease).
Nociceptive pain
The WHO classifies analgesics used for this type of pain on a three-step ladder:
Step 1 : non-opioid analgesics such as paracetamol and nonsteroidal antiinflammatory drugs (NSAIDs). Step 2: weak opioid analgesics such as codeine and tramadol. Their combination with one or two Step 1 analgesics is recommended. The treatment of pain is based on a few fundamental concepts: Step 3: strong opioid analgesics, first and foremost morphine. Their combination with one or two Step 1 analgesics is recommended. Pain can only be treated correctly if it is correctly evaluated. The only person who can evaluate the intensity of pain is the patient himself. The use of pain assessment scales is invaluable. Treatment of pain should be as prompt as possible.
The pain evaluation observations should be recorded in the patient chart in the same fashion as other vital signs. It is recommended to administer analgesics in advance when appropriate (e.g. before painful care procedures). Analgesics should be prescribed and administered at fixed time intervals (not on demand). Oral forms should be used whenever possible. The combination of different analgesic drugs (multimodal analgesia) is advantageous. Start with an analgesic from the level presumed most effective: e.g., in the event of a fractured femur, start with a Step 3 analgesic. The treatment and dose chosen are guided by the assessment of pain intensity, but also by the patients response which may vary significantly from one person to another. Mild pain Treatment of acute pain Paracetamol + /- NSAID
31
Level 1
Level 2
32
Pain
paracetamol PO 50 kg: 15 mg/kg every 6 hours (max. 60 mg/kg/day) > 50 kg: 1 g every 6 hours (max. 4 g/day) 300 mg to 1 g every 4 to 6 hours (max. 3 to 4 g/day) 75 mg once daily 30 to 60 mg every 4 to 6 hours (max. 240 mg/day) 1200 to 1800 mg/day in 3 to 4 divided doses
paracetamol IV
Children
< 10 kg: 7.5 mg/kg every 6 hours (max. 30 mg/kg/day) > 10 kg: 15 mg/kg every 6 hours (max. 60 mg/kg/day)
The efficacy of IV paracetamol is not superior to the efficacy of oral paracetamol; the IV route is restricted to situations where oral administration is impossible.
diclofenac IM
ibuprofen PO
codeine PO
Treatment must be as short as possible. Respect contra-indications. Add a laxative if treatment > 48 hours. 25 to 50 mg every 12 hours in elderly patients and in patients with severe renal or hepatic impairment.
tramadol PO
6 months-12 years: 0.5 to 1 mg/kg every 4 to 6 hours > 12 years: 30 to 60 mg every 4 to 6 hours (max. 240 mg/day)
Analgesics
> 6 months: 1 mg/kg/day in 6 divided 60 mg/day in 6 divideded doses at doses at 4 hour-intervals, to be ajusted 4 hour-intervals, to be ajusted in in relation to pain intensity relation to pain intensity
Children
- Reduce the dose (30 mg/day) in elderly patients and patients with renal or hepatic impairment. - Add a laxative if treatment > 48 hours.
Level 3
morphine SC, IM
The effective daily dose is determined The effective daily dose is determined - Do not initiate treatment with the during the initial treatment with during the initial treatment with sustained release morphine in immediate release morphine (MIR). immediate release morphine (MIR). elderly patients or those with renal or hepatic impairment. Begin If treatment is initiated directly with If treatment is initiated directly with treatment with the immediate MSR: MSR: release morphine (MIR). > 6 months: 1 mg/kg/day in 2 divided 60 mg/day in 2 divided doses at - Add a laxative if treatment doses at 12 hour-intervals, to be ajusted 12 hour-intervals, to be ajusted in > 48 hours. in relation to pain intensity relation to pain intensity - In elderly patients and in patients with severe renal or hepatic impairment: reduce doses by half 0.1 mg/kg administered in fractionated and administer less frequently, doses (0.05 mg/kg every 10 minutes), according to clinical response. to be repeated every 4 hours if - Add a laxative if treatment necessary > 48 hours. 0.1 to 0.2 mg/kg every 4 hours
morphine IV
> 6 months: 0.1 mg/kg administered in fractionated doses (0.05 mg/kg every 10 minutes), to be repeated every 4 hours if necessary
33
Pain
Morphine is an effective treatment for many types of severe pain. Its analgesic effect is dose-dependent. Its adverse effects have often been exaggerated and should not be an obstacle to its use. The most serious adverse effect of morphine is respiratory depression, which may be fatal. This adverse effect results from overdose. It is, therefore, important to increase doses gradually. Respiratory depression is preceded by drowsiness, which is a warning to monitor respiratory rate (RR). The RR should remain equal to or greater than the thresholds indicated below: Neonate Children 1 to 12 months Children 1 to 2 years Children 2 to 5 years RR 35 respirations/min RR 25 respirations/min RR 20 respirations/min RR 15 respirations/min RR 10 respirations/min
Morphine and codeine always cause constipation. A laxative should be prescribed if the opioid treatment continues more than 48 hours. Lactulose PO is the drug of choice: children < 1 year: 5 ml/day; children 1-6 years: 5 to 10 ml/day; children 7-14 years: 10 to 15 ml/day; adults: 15 to 45 ml/day). If the patients stools are soft, a stimulant laxative (bisacodyl PO: children > 3 years: 5 to 10 mg/day; adults: 10 to 15 mg/day) is preferred. Nausea and vomiting are common at the beginning of treatment. Adults: haloperidol PO (2 mg/ml oral solution): 1 to 2 mg to be repeated up to 6 times daily or metoclopramide PO: 15 to 30 mg/day in 3 divided doses with an interval of at least 6 hours between each dose Do not combine haloperidol and metoclopramide. Children: ondansetron PO: 0.15 mg/kg to be repeated up to 3 times daily. Do not exceed 4 mg/dose. Do not use metoclopramide in children.
Respiratory depression must be identified and treated quickly: verbal and physical stimulation of the patient; administration of oxygen; respiratory support (bag and mask) if necessary. If no improvement, administer naloxone (antagonist of morphine) in bolus of 1 to 3 micrograms/kg as necessary until RR normalises and the excessive drowsiness resolves.
For chronic pain in late stage disease (cancer, AIDS etc.), morphine PO is the drug of choice. It may be necessary to increase doses over time according to pain assessment. Do not hesitate to give sufficient and effective doses. Morphine, tramadol and codeine have similar modes of action and should not be combined.
34
Buprenorphine, nalbuphine and pentazocine must not be combined with morphine, pethidine, tramadol or codeine because they have competitive action. Treatment of nociceptive pain in pregnant and breast-feeding women
Analgesics paracetamol aspirin ibuprofen codeine 1st and 2nd trimester 1st choice avoid avoid Pregnancy 3rd trimester and term 1st choice Breast-feeding 1st choice possible avoid
Level 1
contra-indicated The newborn infant may develop withdrawal symptoms, respiratory depression and drowsiness in the event of prolonged administration of large doses at the end of the 3rd trimester. Closely monitor the newborn infant. contra-indicated
possible
Level 2
Use with caution, for a short period (2-3 days), at the lowest effective dose. Monitor the mother and the child: in the event of excessive drowsiness, stop treatment.
tramadol
possible
morphine Level 3
possible
The child may develop drowsiness when the mother receives tramadol at the end of the 3rd trimester and during breast-feeding. Administer with caution, for a short period, at the lowest effective dose, and monitor the child.
The child may develop withdrawal symptoms, respiratory depression and drowsiness when the mother receives morphine at the end of the 3rd trimester and during breast-feeding. Administer with caution, for a short period, at the lowest effective dose, and monitor the child.
Neuropathic pain
amitriptyline PO
Commonly used analgesics are often ineffective in treating this type of pain.
carbamazepine PO Adults: start with a dose of 200 mg once daily at night for one week, then 400 mg/day in 2 divided doses (morning and night) for one week, then 600 mg/day in 3 divided doses. Given its teratogenic risk, carbamazepine should only be used in women of childbearing age when covered by non-hormonal contraception (copper intrauterine device). 35
Adults: start with a dose of 10 to 25 mg/day at night and increase progressively to reach an effective dose, without exceeding 150 mg/day. Reduce the dose by 1/2 in elderly patients.
Pain
Mixed pain
In mixed pain with a significant component of nociceptive pain, such as in cancer or AIDS, morphine is combined with antidepressants and antiepileptics.
Chronic pain
In contrast to acute pain, medical treatment alone is not always sufficient in controlling chronic pain. A multidisciplinary approach including medical treatment, physiotherapy, psychotherapy and nursing is often necessary to allow good pain relief and encourage patient self-management.
Co-analgesics
The combination of certain drugs may be useful or even essential in the treatment of pain: antispasmodics, muscle relaxants, anxiolytics, corticosteroids, local anaesthesia, etc.
36
Anaemia
Anaemia is defined as a haemoglobin level below reference values1. It is a frequent symptom in tropical settings where 10 to 20 % of the population present with Hb levels less than 10 g/dl. Anaemia is caused by: decreased production of red blood cells: nutritional iron and/or folic acid deficiency, depressed bone marrow function, some infections (HIV, visceral leishmaniasis etc.); loss of red blood cells: acute or chronic haemorrhage (ancylostomiasis etc.) increased destruction of red blood cells (haemolysis): malaria; infections or the intolerance of certain drugs by patients with G6PD deficiency (primaquine, dapsone, cotrimoxazole, nalidixic acid, nitrofuran derivatives etc.); haemoglobinopathies (sickle cell disease, thalassaemias); certain bacterial and viral infections (HIV).
In tropical settings, the causes are often interlinked, the two most common causes are nutritional deficiencies and malaria. The groups most at risk are children and young women, particularly during pregnancy. Anaemia in itself is not an indication for transfusion. Most anaemias are well tolerated and can be corrected with simple aetiological treatment.
Clinical features
Common signs of anaemia: pallor of the conjunctivae, mucous membranes, palms of hands and soles of feet; fatigue, dizziness, oedema in the lower limbs, dyspnoea, tachycardia, heart murmur. Look for signs of a specific pathology: cheilosis, nutritional deficiency glossitis, haemolytic jaundice, signs of malaria (see page 131) etc.
Signs that anaemia may be immediately life threatening: sweating, thirst, cold extremities, tachycardia, respiratory distress and shock.
Laboratory
Haemoglobin level (or if haemoglobin is not available, haematocrit) Thick and thin blood films or rapid test if malaria is suspected
1 Normal values: > 13 g/dl in men; > 12 g/dl in women; > 11 g/dl in pregnant women; > 13.5 g/dl in newborns;
> 9.5 g/dl in infants from 2 to 6 months; > 11 g/dl in children from 6 months to 6 years; > 11.5 g/dl in children from 6 to 12 years. 37
Anaemia
Combine with an anthelminthic albendazole PO (except during the first trimester of pregnancy) Children > 6 months and adults: 400 mg as a single dose (Children > 6 months but < 10 kg: 200 mg as a single dose) or mebendazole PO (except during the first trimester of pregnancy) Children > 6 months and adults: 200 mg/day in 2 divided doses for 3 days (Children > 6 months but < 10 kg: 100 mg/day in 2 divided doses for 3 days)
or preferably, give a combination of elemental iron (65 mg) + folic acid (400 g) PO2.
folic acid PO Children under 1 year: 0.5 mg/kg once daily for 4 months Children over 1 year and adults: 5 mg once daily for 4 months
Haemolytic anaemia
Malaria: iron is ineffective except in patients with an associated iron deficiency. For the treatment of malaria, see page 131. G6PD deficiency: no specific treatment; early treatment of infections; stop any drugs suspected to be causing a reaction.
Note: the prevalence of HIV infection makes screening of donors vital. If there is no possibility of screening, it is up to the physician to weigh the transfusion risk with the life or death risk of not transfusing the patient. All transfusions that are not strictly indicated are strictly contra-indicated.
Tablets of 200 mg ferrous sulphate such as those of ferrous sulphate + folic acid contain 65 mg of elemental iron. 300 mg tablets of ferrous gluconate contain 35 mg of elemental iron.
38
Determine the volume of whole blood to be transfused: V = (haemoglobin required minus patients haemoglobin) multiplied by 6 multiplied by patients weight Determine the transfusion rate: (1 ml of whole blood = 15 drops)
Adults
Example: haemoglobin required = 7 g/dl patients haemoglobin = 4 g/dl patients weight = 60 kg Volume in ml = (7 4) x 6 x 60 = 1080 ml Example: 1080 ml to be administered over 3 hours 1080 (ml) 180 (minutes) = 6 ml/minute 6 (ml) x 15 (drops) = 90 drops/minute
Monitor vital signs (pulse, blood pressure, respiratory rate, temperature) and watch for clinical signs of transfusion reactions.
Newborns and children under 1 year: 15 ml/kg over 3 to 4 hours Children over 1 year: 20 ml/kg over 3 to 4 hours Malnourished children: 10 ml/kg over 3 hours
Children
Example: a malnourished child weighing 25 kg 10 (ml) x 25 (kg) = 250 ml over 3 hours 250 (ml) 180 (minutes) = 1.4 ml/minute 1.4 (ml) x 15 (drops) = 21 drops/minute
In some cases, particularly in children suffering from severe malaria, anaemia may cause heart failure which may be decompensated by transfusion. If signs of hypervolaemia are seen: furosemide slow, direct IV: 1 mg/kg without exceeding 20 mg/kg.
Prevention
For patients with sickle cell disease: long term treatment with folic acid PO: 5 mg/day. Early treatment of malaria, helminthic infections etc.
Iron or folic acid deficiency: drug supplements in pregnant woman: elemental iron (65 mg) + folic acid (400 g) PO: 60 mg once daily = 1 tab/day Nutritional supplements if the basic diet is insufficient
39
Marasmus : significant loss of muscle mass and subcutaneous fat, resulting in a skeletal appearance.
Kwashiorkor: bilateral oedema of the lower limbs/oedema of the face, often associated with cutaneous signs (shiny or cracked skin, burn-like appearance; discoloured and brittle hair). The two forms may be associated (marasmic-kwashiorkor). In addition to these characteristic signs, severe acute malnutrition is accompanied by significant physiopathological disorders (metabolic disturbances, anaemia, compromised immunity, leading to susceptibility to infections often difficult to diagnose, etc.). Complications are frequent and potentially life-threatening. Mortality rates may be elevated in the absence of specific medical management. Admission and discharge criteria for treatment programmes for severe acute malnutrition are both anthropometric and clinical: Mid-upper arm circumference (MUAC) is the circumference, measured in midposition, of the relaxed left upper arm, taken in children of 6 to 59 months (65 to 110 cm in height). MUAC measures the degree of muscle wasting. A MUAC of < 115 mm indicates severe malnutrition and significant mortality risk..
The presence of bilateral oedema of the lower limbs (when other causes of oedema have been ruled out) indicates severe malnutrition, regardless of the MUAC and W/H.
1 Some national programmes define anthropometric admission and discharge criteria with reference to NCHS
Weight for height (W/H) index assesses the degree of weight loss by comparing the weight of the malnourished child with non-malnourished children of the same height. Severe malnutrition is defined as a W/H index of < 3Z with reference to the new WHO child growth standards1.
40
Usual discharge (cure) criteria are: W/H > 2Z 2 and absence of bilateral oedema (2 consecutive assessments, one week apart) and absence of acute medical problems.
Usual admission criteria are: MUAC < 115 mm (MUAC is not used as an admission criterion in children older than 59 months or taller than 110 cm) or W/H < 3Z2 or presence of bilateral oedema of the lower limbs.
Medical management (hospitalisation or ambulatory care) is based on the presence or absence of associated serious complications: Children exhibiting anorexia, or significant medical complications, such as severe anaemia, severe dehydration or severe infection (complicated acute malnutrition) should be hospitalised3.
Children without significant medical complications (uncomplicated acute malnutrition) may undergo treatment on an ambulatory basis, with weekly medical follow-up.
Treatment
1) Nutritional treatment Nutritional treatment is based on the use of therapeutic foods enriched with vitamins and minerals: Therapeutic milks (for use exclusively in hospitalised patients): F-75 therapeutic milk, low in protein, sodium and calories (0.9 g of protein and 75 kcal per 100 ml) is used in the initial phase of treatment for patients suffering from complicated acute malnutrition. It is used to cover basic needs while complications are being treated. It is given in 8 daily meals. F-100 therapeutic milk, in which the concentration of protein and calories is higher (2.9 g of protein and 100 kcal per 100 ml), replaces F-75 after several days, once the patient is stabilised (return of appetite, clinical improvement; disappearance or reduction of oedema). The objective is to facilitate rapid weight gain. It can be given with, or be replaced by, RUTF.
RUTF (ready-to-use therapeutic food), i.e. foods which are ready for consumption (for example, peanut paste enriched with milk solids, such as Plumpynut), are used in children treated in both hospital or ambulatory settings. The nutritional composition of RUTF is similar to F-100, but the iron content is higher. It is designed to promote rapid weight gain (approximately 500 kcal per 100 g). RUTF are the only therapeutic foods which can be used in ambulatory treatment.
2 Some national programmes define anthropometric admission and discharge criteria with reference to NCHS
3 As a rule, any malnourished child presenting with medical complications should initially be hospitalised, even if
s/he suffers from moderate, rather than severe, malnutrition (W/H > 3Z).
41
Furthermore, it is important to give drinking water, in addition to meals, especially if the ambient temperature is high or the child has a fever. Breastfeeding should continue in children of the appropriate age. 2) Routine medical treatment
In the absence of specific medical complications, the following routine treatments should be implemented in both ambulatory and hospital settings: Infections Measles vaccination on admission. Broad spectrum antibiotic therapy starting on Day 1 ( amoxicillin PO: 70 to 100 mg/kg/day in 2 divided doses for 5 days)4. In endemic malaria areas: rapid test on D1, with treatment in accordance with results. If testing is not available, give malaria treatment (page 131). Treatment for intestinal worms on D8: albendazole PO Children > 6 months: 400 mg as a single dose (200 mg in children > 6 months but < 10 kg)
Micronutrient deficiencies Therapeutic foods correct most of these deficiencies. 3) Management of common complications Diarrhoea and dehydration
Diarrhoea is common in malnourished children. Therapeutic foods facilitate the recovery of gastrointestinal mucosa and restore the production of gastric acid, digestive enzymes and bile. Amoxicillin, administered as part of routine treatment, is effective in reducing bacterial load. Diarrhoea generally resolves without any additional treatment. Watery diarrhoea is sometimes related to another pathology (otitis, pneumonia, malaria, etc.), which should be considered. If an aetiological treatment is necessary, see page 83.
If a child has a significant diarrhoea (very frequent or abundant stools) but is not dehydrated, administer specific oral rehydration solution (ReSoMal, see below), after each watery stool, to avoid dehydration, according to the WHO treatment Plan A (page 316). However, if the child has no profuse diarrhoea, give plain water (not ReSoMal) after each loose stool.
Dehydration is more difficult to assess in malnourished than healthy children (e.g., delay in return of skin pinch and sunken eyes are present even without dehydration in children with marasmus.).
4 If specific signs of infection are present, the choice of treatment should be directed by the suspected focus. 5 Complete curative treatment with vitamin A is reserved for patients presenting with clinically detectable ocular
42
The diagnosis is made on the basis of a history of watery diarrhoea of recent onset accompanied by weight loss, corresponding to fluid losses since the onset of diarrhoea. Chronic and persistent diarrhoea does not require rapid rehydration. In the event of dehydration: In there is no hypovolaemic shock , rehydration is made by the oral route (if necessary using a nasogastric tube), with specific oral rehydration solution (ReSoMal) 6 , containing less sodium and more potassium than standard solutions. ReSoMal is administered under medical supervision (clinical evaluation and weight every hour). The dose is 20 ml/kg/hour for the first 2 hours, then 10 ml/kg/hour until the weight loss (known or estimated) has been corrected. Give ReSoMal after each watery stool according to the WHO treatment Plan A (page 316). In practice, it is useful to determine the target weight before starting rehydration. The target weight is the weight before the onset of diarrhoea. If the child is improving and showing no signs of fluid overload, rehydration is continued until the previous weight is attained. If the weight loss cannot be measured (e.g. in newly admitted child), it can be estimated at 2 to 5% of the childs current weight. The target weight should not exceed 5% of the current weight (e.g., if the child weighs 5 kg before s t a r t i n g re h y d r a t i o n , t h e t a rg e t w e i g h t s h o u l d n o t e x c e e d 5 . 2 5 0 k g ) . Regardless of the target weight, rehydration should be stopped if signs of fluid overload appear.
In case of hypovolaemic shock (weak and rapid or absent radial pulse, cold extremities, CRT 3 seconds, whether or not consciousness is altered) in a child with diarrhoea or dehydration: Place an IV line and administer 10 ml/kg of 0.9% sodium chloride over 30 minutes, under close medical supervision. Simultaneously: Start broad spectrum antibiotic therapy: ceftriaxone IV 100 mg/kg/day + cloxacillin IV 200 mg/kg/day Administer oxygen (2 litres minimum). Check blood glucose level or administer 5 ml/kg of 10% glucose by slow IV injection. Every 5 minutes, evaluate clinical response (recovery of consciousness, strong pulse, CTR < 3 seconds) and check for signs of over-hydration. - If the clinical condition has improved after 30 minutes, switch to the oral route with ReSoMal: 5 ml/kg every 30 minutes for 2 hours.
6 Except for cholera, in which case standard oral rehydration solutions are used.
43
Bacterial infections
- If the clinical condition has not improved, administer again 10 ml/kg of 0.9% sodium chloride over 30 minutes then, when the clinical condition has improved, switch to the oral route as above. When switching to the oral route, stop the infusion but leave the catheter (capped) in place to keep a venous access, for IV antibiotic therapy.
Lower respiratory infections, otitis, skin and urinary infections are common, but sometimes difficult to identify (absence of fever and specific symptoms). Infection should be suspected in a drowsy or apathetic child. Severe infection should be suspected in the event of shock, hypothermia or hypoglycaemia. Since the infectious focus may be difficult to determine, a broad spectrum antibiotic therapy (cloxacilline + ceftriaxone) is recommended. Hypothermia (rectal temperature < 35.5C or axillary < 35C) is a frequent cause of death in the first days of hospitalisation. Prevention measures include keeping the child close to the mothers body (kangaroo method) and provision of blankets. In case of hypothermia, warm the child as above, monitor the temperature, treat hypoglycaemia. Severe infection should be suspected in the event of hypothermia (see above). In hypoglycaemia, suspected or confirmed (test strip), administer glucose PO if the child is able to drink (50 ml of sugar water [50 ml water + a teaspoon of sugar] or 50 ml of milk); if the child is unconscious, 5 ml/kg of 10% glucose slow IV, to be repeated once if necessary. Treat possible underlying infection.
Oral candidiasis
If the child fails to recover despite appropriate nutritional and medical treatment, consider another pathology: tuberculosis, HIV infection, etc.
Look routinely for oral candidiadis as it interferes with feeding, see treatment page 92.
44
Admission criteria: Adolescents: W/H according to NCHS-CDC-WHO 1982 reference table or bilateral lower limb oedema (Grade 3 or more, having excluded other causes of oedema). Adults: MUAC < 160 mm or bilateral lower limb oedema or MUAC < 185 mm in poor general condition (for example, inability to stand, evident dehydration). As in children, any malnourished patient presenting with significant complications should initially be hospitalised, regardless of the anthropometric criteria above. Discharge criteria: Adolescents: as in children. Adults: weight gain of 10-15% over admission weight and oedema below Grade 2 and good general condition.
Nutritional treatment follows the same principles as in children, but the calorie intake in relation to body weight is lower. Routine treatment is similar to that in children, with the following exceptions: Measles vaccine is only administered to adolescents (up to age 15).
Antibiotics are not routinely given, but infections should be considered, and treated or excluded, in the assessment of the patient.
45
CHAPTER 2
Respiratory diseases
Rhinitis and rhinopharyngitis (common cold) Acute sinusitis Acute laryngitis Diphtheria Otitis 49 50 51 53 55 57 60 62 64 66 73 74 79
Acute pharyngitis
2. Respiratory diseases
Clinical features
Nasal discharge or obstruction, which may be accompanied by sore throat, fever, cough, lacrimation, and diarrhoea in infants. Purulent nasal discharge is not indicative of a secondary bacterial infection. In children under 5 years, routinely check the tympanic membranes to look for an associated otitis media.
Treatment
Antibiotic treatment is not recommended: it does not promote recovery nor prevent complications. Treatment is symptomatic: Clear the nose with 0.9% sodium chloride1. Fever, throat soreness: paracetamol PO for 2 to 3 days (see page 26).
1 For a child: place him on his back, head turned to the side, and instil 0.9% sodium chloride into each nostril.
49
Acute sinusitis
Acute sinusitis
Acute sinusitis is an infection of the sinus mucosa with purulent discharge of nasal (rhinitis, allergies, obstruction) or dental origin. It may develop into chronic sinusitis, particularly in older children and adults.
Clinical features
Facial pain or ache and purulent nasal discharge Older children and adults Peri-orbital pain in frontal sinusitis; facial pain in maxillary and/or ethmoidal sinusitis. Purulent nasal discharge from the side with pain, nasal obstruction and moderate fever. On examination pain on pressure over the forehead, under the upper border of the orbit or cheek, purulent secretions in the meatus and inflammation of the mucosa. The most common causes are Haemophilus influenzae in children under 5 years and pneumococci in patients over 5 years. Type specific to infants and small children Acute ethmoiditis: high fever, inflammation and swelling of the lower eyelids and the bridge of the nose, purulent nasal discharge. Risk of infection spreading to the neighbouring bony structures, orbits and the meninges. The most common causes are Haemophilus influenzae, pneumococci and staphylococci.
Treatment
Nasal irrigation with 0.9% sodium chloride or Ringer Lactate 4 to 6 times/day to clear the airway. Pain and fever: give paracetamol PO (see page 26). Antibiotic treatment, depending on the severity of infection: amoxicillin PO: 80 mg/kg/day in 2 or 3 divided doses for 7 to 10 days For patients allergic to penicillin: erythromycin PO: 30 to 50 mg/kg/day in 2 to 3 divided doses for 7 to 10 days
For sinusitis secondary to dental infection: dental extraction while under antibiotic treatment.
In infants with ethmoiditis, strong antibiotic treatment is necessary: ceftriaxone IM: 100 mg/kg/day in 2 injections for 10 days or, failing that, ampicillin IV: 200 mg/kg/day in 3 or 4 injections until improvement is seen, then change to oral treatment with amoxicillin PO: 100 mg/kg/day in 2 or 3 divided doses to complete 10 days of treatment
50
2. Respiratory diseases
Acute laryngitis
Laryngitis is an acute infection of the laryngeal mucosa of viral or sometimes bacterial origin.
Inspiratory dyspnoea with cough and hoarse voice. Chest indrawing and stridor may be present. Signs of serious illness: sweating, tachycardia, cyanosis, altered level of consciousness. Examine children in a sitting position. Do not lay children down: there is a risk of respiratory airway obstruction.
Acute laryngitis
Nasal irrigation with 0.9% sodium chloride or Ringer Lactate, 4 to 6 times/day to clear the airway. An antihistamine may be given for 3 days (promethazine PO or chlorphenamine PO, see page 117). In children with severe dyspnoea: dexamethasone IM: 0.1 to 0.2 mg/kg as a single dose or hydrocortisone IM: 1 mg/kg as a single dose
Note: exclude diphtheria (see Diphtheria, page 55) and retropharyngeal abscess.
Viral subglottitis: the onset is frequently nocturnal, the dyspnoea is typical, the cry and cough have a raucous sound, but expiration is unobstructed. Monitor the child, try to keep him calm. Have him breathe in a humid environment (near a bowl of water or wet towel). dexamethasone IM: 0.1 to 0.2 mg/kg or hydrocortisone IM: 1 mg/kg, to be repeated after 30 minutes if necessary Antibiotics are not useful, except in cases of secondary infection (amoxicillin or cotrimoxazole). In case of deterioration: intubation if possible, or, failing that, tracheotomy.
Adults
Very rarely, epiglottitis due to Haemophilus influenzae, diphtheria or retropharyngeal abscess: same clinical signs and treatment as for children.
Also consider laryngeal tuberculosis in a patient with tuberculosis, or cancer of the larynx, particularly if the patient smokes.
52
2. Respiratory diseases
Acute pharyngitis
Acute inflammation of the tonsils and pharynx. The majority of cases are of viral origin and do not require antibiotic treatment. Group A streptococcus is the main bacterial cause, and mainly affects children age 3 to 14 years. Acute rheumatic fever, a serious late complication of streptococcal pharyngitis, is common in developing countries, and can be prevented with antibiotic therapy. One of the main objectives in assessing acute pharyngitis is to identify patients requiring antibiotic treatment.
Clinical features
Features common to all types of pharyngitis: Throat pain and dysphagia (difficulty swallowing), with or without fever.
Specific features, depending on the cause: Common forms: Erythematous (red throat) or exudative (red throat and whitish exudate) pharyngitis: Since this appearance is common to both viral and streptococcal pharyngitis, other criteria should be considered to distinguish between them: In children under 3 years, streptococcal pharyngitis is rare and pharyngitis is almost exclusively viral. In children from 3 to 14 years, the presence of at least 3 of the 4 following features [absence of cough, fever above 38C, at least one enlarged and tender anterior cervical lymph node, presence of an exudate] favours streptococcal pharyngitis. Conversely, presence of cough, runny nose, conjunctivitis or enlarged posterior cervical lymph nodes favours viral pharyngitis. In patients over 14 years, the probability of streptococcal pharyngitis is low. Infectious mononucleosis (IM) due to the Epstein-Barr virus should be suspected in adolescents and young adults with extreme fatigue, generalized adenopathy and often splenomegaly. Erythematous or exudative pharyngitis may also be associated with gonococcal or primary HIV infection. In these cases, the diagnosis is mainly prompted by the patient's history. Pseudomembranous pharyngitis (red tonsils/pharynx covered with an adherent grayish white false membrane): see diphtheria, page 55. Less common forms: Vesicular pharyngitis (clusters of tiny blisters on the tonsils): always viral (coxsackie virus or primary herpetic infection). Ulcero-necrotic pharyngitis : hard and painless syphilitic chancre of the tonsil; tonsillar ulcer soft on palpation in a patient with poor oral hygiene and malodorous breath (Vincent tonsillitis). Local complications: Peritonsillar abcess: fever, intense pain, hoarse voice, trismus (limitation of mouth opening), unilateral deviation of the uvula.
53
Acute pharyngitis
Treatment
Treat fever and pain in all cases (paracetamol PO, page 26)
Viral pharyngitis is usually a self-limited illness. Spontaneous resolution typically occurs within a few days (or weeks, for IM): no antibiotic therapy.
Vincent tonsillitis: penicillin V or erythromycin as above Peritonsillar abscess: refer for surgical drainage
Gonococcal or syphilitic pharyngitis: same treatment as for genital gonorrhoea and syphilis
Choice of antibiotic treatment for streptococcal pharyngitis: If single-use injection equipment is available, benzathine benzylpenicillin is the drug of choice as streptococcus A resistance to penicillin remains rare; it is the only antibiotic proven effective in reducing the incidence of rheumatic fever; and the treatment is administered as a single dose. benzathine benzylpenicilin IM Children under 6 years: 600 000 IU as a single dose Children over 6 years and adults: 1.2 MIU as a single dose Penicillin V is the oral reference treatment, but poor adherence is predictable due to the length of treatment. phenoxymethylpenicilin (penicillin V) PO for 10 days Children under 1 year: 250 mg/day in 2 divided doses Children from 1 to 5 years: 500 mg/day in 2 divided doses Children from 6 to 12 years: 1 g/day in 2 divided doses Adults: 2 g/day in 2 divided doses Amoxicillin is an alternative and the treatment has the advantage of being relatively short. However, it can cause adverse skin reactions in patients with undiagnosed IM and thus should be avoided when IM has not been excluded. amoxicillin PO for 6 days Children: 50 mg/kg/day in 2 divided doses Adults: 2 g/day in 2 divided doses Resistance to macrolides is frequent, erythromycin and azithromycin should be reserved for penicillin allergic patients. Poor adherence with erythromycin is predictable due to the length of treatment. Azithromycin treatment has the advantage of being short. erythromycin PO for 10 days Children: 30 to 50 mg/kg/day in 2 to 3 divided doses Adults: 2 to 3 g/day in 2 to 3 divided doses or azithromycin PO for 3 days Children: 20 mg/kg once daily Adults: 500 mg once daily
54
2. Respiratory diseases
Diphtheria
Diphtheria is a bacterial infection due to Corynebacterium diphtheriae, characterized by local proliferation (most commonly ENT) of the bacteria, and systemic diffusion of the diphtheria toxin through the body. Transmission is by direct contact with an infected person.
Clinical features
Incubation period: 3 to 5 days Local signs: febrile tonsillitis with pseudomembranes (grey, tough and very sticky false membranes) sometimes accompanied by signs of serious illness: high fever (greater than 39C), oliguria, cervical oedema, enlarged cervical lymph glands and signs of haemorrhage (cervical or thoracic purpura, gingival bleeding, epistaxis). laryngitis, most commonly secondary to the tonsillitis. Risk of death by asphyxiation. other local signs: rhinitis (often unilateral); secondary infection of a skin lesion with C. diphtheriae. General signs due to the toxin: mycocarditis: clinically detectable arrhythmias or cardiac conduction defects in 25% of patients. These are more serious when appear early (from the 5th day). neuropathies may occur 1 to 3 months after the onset of the disease: paralysis of the soft palate, respiratory muscles, limbs and accommodation. more rarely: pneumonia, renal failure with oligo-anuria and haematuria.
Laboratory
Confirmation is made by isolating the toxic strain of C. diphtheriae from a throat swab.
Strict isolation. Treatment with antitoxin serum: do not wait for bacteriological confirmation. For diphtheria antitoxin derived from horse serum, administer according to the Besredka method1. Doses are given as a function of the severity of illness, and the delay in treatment:
Laryngitis or pharyngitis Rhinopharyngitis Serious forms or if treatment is started more than 48 hours after onset of symptoms 40 000 to 60 000 80 000 and up to 100 000 20 000 to 40 000 Dose in units Depends on the volume to be administered: IM or for volumes greater than 20 000 units IV infusion in 200 ml 0.9% NaCl, over one hour Administration route
1 Besredka method: inject 0.1 ml SC and wait 15 minutes. If there is no allergic reaction (no erythema at the injection
site or a flat erythema of less than 0.5 in diameter, inject a further 0.25 ml SC. If there is no reaction after 15 minutes, inject the rest of the product IM or IV depending on the volume to be administered. 55
Diphtheria
Antibiotic treatment:
benzathine benzylpenicillin IM Children under 6 years: 600 000 IU as a single dose Children over 6 years and adults: 1.2 MIU as a single dose or procaine benzylpenicillin IM Children: 50 000 IU/kg once daily for 7 days Adults: 1.2 MIU once daily for 7 days erythromycin PO
Urgent intervention to secure an airway (intubation, tracheotomy) may be necessary in the event of laryngeal obstruction or cardiac or neurologic complications. Nose and throat cultures. Quarantine
Children: 50 mg/kg/day in 2 to 3 divided doses for 7 days Adults: 2 to 3 g/day in 2 to 3 divided doses for 7 days
Daily clinical monitoring (throat examination and temperature) for 7 days. Antibiotic treatment: see above. Verify vaccination status: less than 3 injections: complete with DTP, DT or Td depending on age, 3 injections: if the last injection was given more than one year before, give a booster dose. The same precautions should be taken for contacts of healthy carriers.
Prevention
There are 3 combined vaccines: DTP: diphtheria-tetanus-pertussis DT: diphtheria (30 IU) and tetanus, for those under 7 years of age Td: diphtheria (3 IU) and tetanus, for those over 7 years of age
In the event of an epidemic, mass vaccination: Update routine vaccinations with DTP for children under 3 years of age; DT for children from 3 to 6 years of age; Td for children over 7 years of age and adults.
Routine vaccination (EPI). The recommendations vary according to the country. For information: DTP: 3 doses at one month intervals before the age of 1 year, DTP booster one year later, and DT at 6 years of age followed by 3 more boosters at 10 year intervals.
Note: the disease does not give immunity. Update the vaccination of the patients once they have recovered. Vaccination does not prevent individuals from becoming carriers.
56
2. Respiratory diseases
Otitis
Acute otitis externa
2
Diffuse inflammation of the external ear canal, due to bacterial or fungal infection. Common precipitants of otitis externa are maceration, trauma of the ear canal or presence of a foreign body or dermatologic diseases (such as eczema, psoriasis).
Clinical features
Ear canal pruritus or ear pain, often severe and exacerbated by motion of the pinna; feeling of fullness in the ear; clear or purulent ear discharge or no discharge Otoscopy: diffuse erythema and edema, or infected eczema, of the ear canal look for a foreign body if visible, the tympanic membrane is normal (swelling, pain or secretions very often prevent adequate visualization of the tympanic membrane)
Treatment
Remove a foreign body, if present. Treatment of pain: paracetamol and/or ibuprofen PO (page 29). Local treatment (usually 5 to 7 days): Remove skin debris and secretions from the auditory canal by gentle dry mopping (use a dry cotton bud or a small piece of dry cotton wool). In addition, 0.5% gentian violet can be applied once a day, using a cotton bud. Consider ear irrigation (0.9% sodium chloride, using a syringe) only if the tympanic membrane can be fully visualised and is intact (no perforation). Otherwise, ear irrigation is contra-indicated.
Acute inflammation of the middle ear, due to viral or bacterial infection, very common in children under 3 years, but uncommon in adults. The principal causative organisms of bacterial otitis media are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and in older children, Streptococcus pyogenes.
Clinical features
Rapid onset of ear pain (in infants: crying, irritability, sleeplessness, reluctance to nurse) and ear discharge (otorrhoea) or fever. Other signs such as rhinorrhoea, cough, diarrhoea or vomiting are frequently associated, and may confuse the diagnosis, hence the necessity of examining the tympanic membranes.
57
Otitis
Otoscopy: bright red tympanic membrane (or yellowish if rupture is imminent) and presence of pus, either externalised (drainage in ear canal if the tympanic membrane is ruptured) or internalised (opaque or bulging tympanic membrane). The combination of these signs with ear pain or fever confirms the diagnosis of AOM. Note: The following otoscopic findings are not sufficient to make the diagnosis of AOM: A red tympanic membrane alone, with no evidence of bulging or perforation, is suggestive of viral otitis in a context of upper respiratory tract infection, or may be due to prolonged crying in children or high fever. The presence of air bubbles or fluid behind an intact tympanic membrane, in the absence of signs and symptoms of acute infection, is suggestive of otitis media with effusion (OME). Complications, particularly in high-risk children (malnutrition, immunodeficiency, ear malformation) include chronic suppurative otitis media, and rarely, mastoiditis, brain abscess or meningitis.
Treatment
In all cases: Treatment of pain and fever: paracetamol PO, page 26. Ear irrigation is contra-indicated if the tympanic membrane is ruptured, or when the tympanic membrane cannot be fully visualised. Ear drops are not indicated.
Indications for antibiotic therapy: Antibiotics are prescribed in children less than 2 years, children whose assessment suggests severe infection (vomiting, fever > 39C, severe pain) and children at risk of unfavourable outcome (malnutrition, immunodeficiency, ear malformation). For other children: 1) If the child can be re-examined within 48 to 72 hours: it is preferable to delay antibiotic prescription. Spontaneous resolution is probable and a short symptomatic treatment of fever and pain may be sufficient. Antibiotics are prescribed if there is no improvement or worsening of symptoms after 48 to 72 hours. 2) If the child cannot be re-examined: antibiotics are prescribed. For children treated with antibiotics: advise the mother to bring the child back if fever and pain persist after 48 hours. Choice of antibiotic therapy: Amoxicillin is the first-line treatment: amoxicillin PO: Children: 80 to 100 mg/kg/day in 3 divided doses for 5 days Adults: 1500 mg/day in 3 divided doses for 5 days
Amoxicillin/clavulanic acid is used as second-line treatment, in the case of treatment failure. Treatment failure is defined as persistence of fever and/or ear pain after 48 hours of antibiotic treatment. amoxicillin/clavulanic acid (co-amoxiclav) PO for 5 days The dose is expressed in amoxicillin: Children < 40 kg: 45 to 50 mg/kg/day in 2 divided doses (if using ratio 8:1 or 7:1) or in 3 divided doses (if using ratio 4:1) Note: the dose of clavulanic acid should not exceed 12.5 mg/kg/day or 375 mg/day.
58
2. Respiratory diseases
Persistence of a ear drainage alone, without fever and pain, in a child who has otherwise improved (reduction in systemic symptoms and local inflammation) does not warrant a change in antibiotic therapy. Clean ear canal by gentle dry mopping until no more drainage is obtained. Azithromycin or erythromycin should be reserved for very rare penicillin-allergic patients, as treatment failure (resistance to macrolides) is frequent. azithromycin PO Children over 6 months: 10 mg/kg once daily for 3 days erythromycin PO 30 to 50 mg/kg/day in 2 to 3 divided doses for 10 days
Children 40 kg and adults: 1500 to 2000 mg/day depending on the formulation available: Ratio 8:1: 2000 mg/day = 2 tablets of 500/62.5 mg 2 times per day Ratio 7:1: 1750 mg/day = 1 tablet of 875/125 mg 2 times per day Ratio 4:1: 1500 mg/day = 1 tablet of 500/125 mg 3 times per day Note: the dose of clavulanic acid should not exceed 375 mg/day.
Chronic bacterial infection of the middle ear with persistent purulent discharge through a perforated tympanic membrane. The principal causative organisms are Pseudomonas aeruginosa , Proteus spp , staphylococcus, other Gram negatives and anaerobes.
Clinical features
Purulent discharge for more than 2 weeks, often associated with hearing loss or even deafness; absence of pain and fever Otoscopy: perforation of the tympanic membrane and purulent exudate Complications: Consider a superinfection (AOM) in the case of new onset of fever with ear pain, and treat accordingly. Consider mastoiditis in the case of new onset of high fever, severe ear pain and/or tender swelling behind the ear, in a patient who appears significantly unwell. Consider brain abscess or meningitis in the case of impaired consciousness, neck stiffness and focal neurological signs (e.g. facial nerve paralysis).
Treatment
Remove secretions from the auditory canal by gentle dry mopping (use a dry cotton bud or a small piece of dry cotton wool) then apply ciprofloxacin (ear drops): 2 drops twice daily, until no more drainage is obtained (max. 4 weeks). Complications: Chronic mastoiditis is a medical emergency that requires prompt hospitalisation, prolonged antibiotic treatment that covers the causative organisms of CSOM (ceftriaxone IM 10 days + ciprofloxacin PO for 14 days), atraumatic cleaning of the ear canal; surgical treatment may be required. Before transfer to hospital, if the patient needs to be transferred, administer the first dose of antibiotics. Meningitis: see page 165.
59
Clinical features
After an incubation period of 7 to 10 days, the illness evolves in 3 phases: Catarrhal phase (1 to 2 weeks): coryza and cough. At this stage, the illness is indistinguishable from a minor upper respiratory infection. Paroxysmal phase (1 to 6 weeks): Typical presentation: cough of at least 2 weeks duration, occurring in characteristic bouts (paroxysms), followed by a laboured inspiration causing a distinctive sound (whoop), or vomiting. Fever is absent or moderate, and the clinical exam is normal between coughing bouts; however, the patient becomes more and more fatigued. Atypical presentations: - Infants under 6 months: paroxysms are poorly tolerated, with apnoea, cyanosis; coughing bouts and whoop may be absent. - Adults: prolonged cough, often without other symptoms. Complications: - Major: in infants, secondary bacterial pneumonia (new-onset fever is an indicator); malnutrition and dehydration triggered by poor feeding due to cough and vomiting; rarely, seizures, encephalopathy; sudden death. - Minor: subconjunctival haemorrhage, petechiae, hernias, rectal prolapse Convalescent phase: symptoms gradually resolve over weeks or months.
2. Respiratory diseases
Hydration and nutrition: ensure children < 5 years are well hydrated; breastfeeding should continue. Advise mothers to feed the child frequently in small quantities after coughing bouts and the vomiting which follows. Monitor the weight of the child during the course of the illness, and consider food supplements for several weeks after recovery.
Antibiotic therapy: Antibiotic treatment is indicated in the first 3 weeks after onset of cough. Infectivity is virtually nil after 5 days of antibiotic treatment.
azithromycin PO
Antibiotic
First line
Alernative
0-5 months: D1 500 mg 10 mg/kg/day D2-D5 250 mg/day 6 months: D1 10 mg/kg (max 500 mg) D2-D5 5 mg/kg/d (max 250 mg/d) 50 mg/kg/day (avoid in infant < 1 month of age) 1 g/day
Children
Adults
For hospitalised children: Place the child in a semi-reclining position ( 30). Oro-pharyngeal suction if needed. Post-exposure prophylaxis
40 mg/kg/day SMX 1600 mg/day SMX + 8 mg/kg/day TMP + 320 mg/day TMP (avoid in infant < 1 month of age, and last month of pregnancy)
Antibiotic prophylaxis (same treatment as for suspect cases) is recommended for unvaccinated or incompletely vaccinated infants of less than 6 months, who have had contact with a suspect case. Isolation of contacts is not necessary.
Note: pertussis vaccination should be updated in all cases (suspects and contacts). If the primary series has been interrupted, it should be completed, rather than restarted from the beginning.
Prevention
Routine vaccination with polyvalent vaccines containing pertussis antigens (e.g. DTP, or DTP + Hep B, or DTP + Hib + Hep B) from the age of 6 weeks or according to national protocol. Neither vaccination nor natural disease confers lasting immunity. Booster doses are necessary to reinforce immunity and reduce the risk of developing disease and transmitting it to young children.
61
Bronchitis
Bronchitis
Acute bronchitis
An acute inflammation of the bronchial mucosa, most commonly of viral origin. In older children it can be caused by Mycoplasma pneumoniae. In children over 2 years of age with repetitive acute bronchitis or wheezing bronchitis, consider asthma (see Asthma , page 74). In children under 2 years of age, consider bronchiolitis (see Bronchiolitis, page 64).
Clinical features
Often begins with a rhinopharyngitis that descends progressively: pharyngitis, laryngitis, tracheitis. Heavy cough, dry at the beginning then becoming productive Low-grade fever No tachypnoea, no dyspnoea On pulmonary auscultation: bronchial wheezing
Treatment
Keep the patient hydrated, humidify air (with a bowl of water or a wet towel).
Children: nasal irrigation with 0.9% sodium chloride or Ringer Lactate, 4 to 6 times/day to clear the airway. Antibiotic treatment is not useful for patients in good overall condition with rhinopharyngitis or influenza. Antibiotic treatment is indicated only if: the patient is in poor general condition: malnutrition, measles, rickets, severe anaemia, cardiac disease, elderly patient etc. if the patient has dyspnoea, fever greater than 38.5C and purulent expectorations: a secondary infection with Haemophilus influenzae or with pneumococcus is probable. Children: 100 mg/kg/day in 3 divided doses for 5 days Adults: 3 g/day in 3 divided doses for 5 days or chloramphenicol PO Adults: 3 g/day in 3 divided doses for 5 days
amoxicillin PO
62
2. Respiratory diseases
Chronic bronchitis
A chronic inflammation of the bronchial mucosa due to irritation (tobacco, pollution), allergy (asthma) or infection (repetitive acute bronchitis). It may develop into chronic obstructive pulmonary disease.
Clinical features
Productive cough for 3 consecutive months per year for 2 successive years. No dyspnoea at onset. Dyspnoea develops after several years, first on exertion, then becoming persistent. On pulmonary auscultation: bronchial wheeze (always exclude tuberculosis). A patient with an acute exacerbation of chronic bronchitis presents with: Onset or increase of dyspnoea Increased volume of sputum Purulent sputum
Treatment
Antibiotic treatment is not useful in treating simple chronic bronchitis. Discourage smoking and other irritating factors.
Antibiotic treatment may be useful, for patients in a poor general condition only, for acute exacerbations of chronic bronchitis (see Acute bronchitis, previous page).
63
Bronchiolitis
Bronchiolitis
Bronchiolitis is an epidemic and seasonal viral infection of the lower respiratory tract in children less than 2 years of age, characterised by bronchiolar obstruction. Respiratory syncytial virus (RSV) is responsible for 70% of cases of bronchiolitis. Transmission of RSV is direct, through inhalation of droplets (coughing, sneezing), and indirect, through contact with hands or materials contaminated by infected secretions. In the majority of cases, bronchiolitis is benign, resolves spontaneously (relapses are possible), and can be treated on an outpatient basis. Severe cases may occur, which put the child at risk due to exhaustion or secondary bacterial infection. Hospitalisation is necessary when signs/criteria of severity are present (10 to 20% of cases).
Clinical features
Tachypnoea, dyspnoea, wheezing, cough; profuse, frothy, obstructive secretions. On auscultation: prolonged expiration with diffuse, bilateral wheezes; sometimes diffuse fine, end-inspiratory crackles. Rhinopharyngitis, with dry cough, precedes these features by 24 to 72 hours; fever is absent or moderate.
Signs of severity: Significant deterioration in general condition, toxic appearance (pallor, greyish colouration) Apnoea, cyanosis (check lips, buccal mucosa, fingernails) Respiratory distress (nasal flaring, sternal and chest wall indrawing) Anxiety and agitation (hypoxia), altered level of consciousness Respiratory rate > 60/min Decreased respiratory distress and slow respirations (< 30/min below the age of 1 year and < 20/min below the age of 3 years, exhaustion). Exercise caution in interpreting these signs as indicators of clinical improvement. Sweats, tachycardia at rest and in the absence of fever Silence on auscultation (severe bronchospasm) Difficulty drinking or sucking (reduced tolerance for exertion)
Treatment
Treatment is symptomatic. Obstructive signs and symptoms last for about 10 days; cough may persist for 2 weeks longer. Hospitalise children with one of the following criteria: Presence of any sign of severity Pre-existing pathology (cardiac or pulmonary disease, malnutrition, HIV, etc.) Consider hospitalisation on a case-by-case basis in the following situations: Associated acute pathology (viral gastro-enteritis, bacterial infection, etc.) Age less than 3 months
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2. Respiratory diseases
In all other cases, the child may be treated at home, provided the parents are taught how to carry out treatment, and what signs of severity should lead to re-consultation. Outpatient treatment Nasal irrigation with 0.9% NaCl before each feeding (demonstrate the technique to the mother)1. Small, frequent feedings to reduce vomiting triggered by bouts of coughing. Increased fluids if fever and/or significant secretions are present. Treat fever (see page 26). Handle the patient the patient as little as possible and avoid unnecessary procedures. Hospitalisation In all cases: Place the infant in a semi-reclining position ( 30). Nasal irrigation, small, frequent feeds, treatment of fever: as for outpatient treatment. Gentle oro-pharyngeal suction if needed. Monitor fluid intake: normal requirements are 80 to 100 ml/kg/day + 20 to 25 ml/kg/day with high fever or very profuse secretions.
According to symptoms: Humidified nasal oxygen (1 to 2 litres/min). When there is vomiting or significant fatigue when sucking, fluid requirements may be administered by nasogastric tube (small volumes on a frequent basis) or the IV route, for the shortest possible time. Avoid breastfeeding or oral feeds in children with severe tachypnoea, but do not prolong NG feeds (respiratory compromise) or IV infusions any longer than necessary. Bronchodilator therapy: this therapy may be considered after a trial treatment has been given (salbutamol inhaler, 100 micrograms/puff: 2 to 3 puffs with spacer, repeated twice at an interval of 30 minutes). If inhaled salbutamol appears effective in relieving symptoms, the treatment is continued (2 to 3 puffs every 6 hours in the acute phase, then gradual reduction as recovery takes place). If the trial is ineffective, the treatment is discontinued. Antibiotics are not indicated unless there is concern about complications such as secondary bacterial pneumonia. Prevention and control The risk of transmission of the virus is increased in hospital settings: Children with bronchiolitis should be grouped together, away from other children (cohorting). As infection is most commonly transmitted by the hands, the most important prevention measure is hand-washing after any contact with patients, and objects or surfaces in contact with patients on which the virus may survive for several hours. In addition, staff should wear gowns, gloves and surgical masks when in contact with patients.
2 Lie the child on his back, head turned to the side and instil 0.9% NaCl into the nose, one nostril at a time.
65
Acute pneumonia
Acute pneumonia
Acute pneumonia is a viral, bacterial (pneumococcus, Haemophilus influenzae , staphylococcus, atypical bacteria) or parasitic (pneumocystosis) infection of the pulmonary alveoli.
The most common causes are viruses, pneumococcus and Haemophilus influenzae.
Clinical examination must be done on a calm child in order to correctly count the respiratory rate and look for signs of serious illness. Pneumonia should be suspected in a child who presents with cough or difficulty breathing. Fever is often high (> 39C), but the child may present with low-grade fever or may have no fever (often a sign of serious illness). The respiratory rate (RR) should be measured over 1 minute. A child has tachypnoea (increased respiratory rate) if: RR 60 breaths/minute in children under 2 months RR 50 breaths/minute in children from 2 to 11 months RR 40 breaths/minute in children from 12 months to 5 years On pulmonary auscultation: dullness with diminished vesicular breath sounds, crepitations and sometimes bronchial breathing or normal pulmonary auscultation.
Clinical features
Signs of serious illness (severe pneumonia) include: Chest indrawing: the inferior thoracic wall depresses on inspiration as the superior abdomen expands Cyanosis (lips, oral mucosa, fingernails) or O2 saturation < 90% Nasal flaring Altered consciousness (child is abnormally sleepy or difficult to wake) Stridor (hoarse noise on inspiration) Grunting (a short repetitive noise produced by a partial closure of the vocal cords) on expiration Refusal to drink or feed Children under 2 months Severe malnutrition Notes: In malnourished children, the RR thresholds should be decreased by 5 breaths/minute from those listed above. Chest indrawing is significant if it is clearly visible and present at all times. If it is observed when a child is upset or feeding and is not visible when the child is resting, there is no chest indrawing. In children under 2 months of age, moderate chest indrawing is normal as the thoracic wall is flexible.
66
2. Respiratory diseases
If only the soft tissues between the ribs or above the clavicles depress, there is no chest indrawing. Consider also: Malaria in endemic areas, as it may also cause cough and tachypnoea. Staphylococcal pneumonia (see page 73) in patients with empyema or painful abdominal swelling and diarrhoea. Pneumocystosis in patients with confirmed or suspected HIV infection (page 215). Tuberculosis: in a child with cough, fever and poor weight gain and a history of close contact with a tuberculous patient 1 . For the diagnosis, refer to the MSF handbook, Tuberculosis. in the event of pneumonia complicated with empyema (pus in the pleural space). Diagnosis of pneumonia in children under 5 presenting with cough or difficulty breathing: Chest indrawing present? with ou without other signs of serious illness
NO
YES
Increased RR?
Severe pneumonia
NO
YES
RR 60 breaths/minute
Pneumonia
1 Contact is defined as living in the same household, or in close and regular contact with any known or suspected
67
Acute pneumonia
Treatment
If penicillins are not available, alternatives may be cefotaxime slow IV (over at least 3 minutes) or infusion (over at least 20 minutes) or IM: 150 mg/kg/day in 3 divided doses for 10 days, or, as a last resort: ceftriaxone slow IV2 (over at least 3 minutes) or infusion (over 30 minutes; 60 minutes in neonates) or IM: 50 mg/kg once daily for 10 days. If the child's condition does not improve3 after 48 hours of well administered treatment, add cloxacillin IV* for 10 to 14 days Children < 7 days Children 7 days > 2 kg cloxacillin 75 mg/kg/day in 3 divided doses 2 kg cloxacillin 75 mg/kg/day in 3 divided doses 2 kg cloxacillin 50 mg/kg/day in 2 divided doses
benzylpenicillin procain IM, 50 000 IU/kg once daily (50 mg/kg once daily) for 10 days (combined with gentamicin IM as above), may be an alternative to ampicillin in contexts where ampicillin cannot be properly administered. However ampicillin remains the drug of choice. Benzylpenicillin procain must NEVER be administered by IV route.
* Each dose is to be administered in 100 ml of 0.9% sodium chloride. Children from 2 months to 5 years of age
The first line treatment is: ceftriaxone IM or slow IV2 (over at least 3 minutes): 50 mg/kg once daily or, if not available: ampicillin IV or IM: 200 mg/kg/day in 3 to 4 divided doses + gentamicin IM: 7.5 mg/kg once daily
2 The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must 3 Improvement criteria include: fever reduction, diminished respiratory distress, improved O saturation, improved 2
never be administered by IV route. For IV administration, water for injection must always be used. appetite and/or activity.
68
2. Respiratory diseases
If the child's condition deteriorates or does not improve4 after 48 hours of correct administration, add cloxacillin IV: 100 mg/kg/day in 4 divided doses. After clinical improvement and 3 days with no fever, switch to the oral route with amoxicillin/clavulanic acid (co-amoxiclav) PO to complete 10 to 14 days of treatment: The dose is expressed in amoxicillin: 100 mg/kg/day in 2 divided doses (if using formulations in a ratio of 8:1 or 7:1)5 Note: the dose of clavulanic acid should not exceed 12.5 mg/kg/day or 375 mg/day. If tuberculosis is unlikely, continue with ceftriaxone + cloxacillin and add azithromycin (see Atypical pneumonia, page 72). Notes: For malnourished children, refer to specific protocol. In the event of moderate-large empyema, assess if drainage is required. Administer antibiotics active against pneumococci and staphylococci (see page 73). Adjuvant therapy
The treatment is administered by parenteral route for at least 3 days then, if the clinical condition has improved4 and oral treatment can be tolerated, switch to the oral route with amoxicillin PO: 100 mg/kg/day in 3 divided doses, to complete 10 days of treatment.
If the child's condition does not improve after 48 hours with ceftriaxone + cloxacillin, consider tuberculosis. For the diagnosis, refer to the MSF handbook, Tuberculosis.
Fever: paracetamol PO (see Fever, page 26). Infants: keep warm. Install on an incline (head elevated) or in semi-sitting position. Clear the airway (nasal irrigation with 0.9% sodium chloride if needed). Oxygen at the flow rate required to maintain SpO2 90% or, if pulse oxymeter is not available, minimum 1 litre/minute. Maintain adequate hydration and nutrition: In children with severe respiratory difficulty: place an IV line and give 70% of normal maintenance fluids. Resume oral feeding as soon as possible (no severe respiratory difficulty, ability to eat normally). Use a nasogastric tube only if an IV line cannot be established: children under 12 months: 5 ml/kg/hour; children over 12 months: 3 to 4 ml/kg/hour; alternate milk and water. Resume normal oral feeding as soon as possible. In the absence of severe respiratory difficulty: breastfeed on demand; milk/food and water by spoon on demand. ORS when required (see dehydration, pages 315 to 320).
69
Acute pneumonia
Follow-up in 48 to 72 hours or sooner if the childs condition deteriorates: if the condition is improving6: continue with the same antibiotic to complete treatment. if there is no improvement after 3 days of correct administration: add azithromycin (see Atypical pneumonia, page 72). if the condition is deteriorating: hospitalise and treat as severe pneumonia.
The most common causes are viruses, pneumococcus, and Mycoplasma pneumoniae. Cough, with or without purulent sputum, fever, thoracic pain, tachypnoea On pulmonary auscultation: decreased vesicular breath sounds, dullness, localised foci of crepitations, sometimes bronchial wheeze. Signs of serious illness (severe pneumonia) include: cyanosis (lips, oral mucosa, fingernails) nasal flaring intercostal or subclavial indrawing RR > 30 breaths/minute heart rate > 125 beats/minute altered level of consciousness (drowsiness, confusion)
Sudden onset with high fever (higher than 39C), thoracic pain and oral herpes are suggestive of pneumococcal infection. Symptoms may be confusing, particularly in children with abdominal pain, meningeal syndrome, etc.
Patients at risk include the elderly, patients suffering from heart failure, sickle cell disease or severe chronic bronchitis; immunocompromised patients (severe malnutrition, HIV infection with CD4 < 200).
Treatment
Children: 50 000 IU/kg once daily Adults: 1.5 MIU once daily Benzylpenicillin procain must NEVER be administered by IV route. The treatment is given by parenteral route for at least 3 days then, if the clinical condition has improved6 and oral treatment can be tolerated, switch to the oral route with amoxicillin PO to complete 7 to 10 days of treatment: Children: 100 mg/kg/day in 3 divided doses Adults: 3 g/day in 3 divided doses
6 Improvement criteria include: fever reduction, diminished respiratory distress, improved O saturation, improved 2
70
2. Respiratory diseases
If the clinical condition deteriorates or does not improve after 48 hours of correct administration, administer ceftriaxone as above + cloxacillin IV: Children: 100 mg/kg/day in 4 divided doses Adults: 8 g/day in 4 divided doses After clinical improvement and 3 days with no fever, switch to the oral route with amoxicillin/clavulanic acid (co-amoxiclav) PO to complete 10 to 14 days of treatment: The dose is expressed in amoxicillin: Children: 100 mg/kg/day in 2 divided doses (if using formulations in a ratio of 8:1 or 7:1)9 Note: the dose of clavulanic acid should not exceed 12.5 mg/kg/day or 375 mg/day. Adults: 2.5 to 3 g/day in 3 divided doses. Depending on the formulation of coamoxiclav available: Ratio 8:1: 3000 mg/day = 2 tablets of 500/62.5 mg 3 times per day Ratio 7:1: 2625 mg/day = 1 tablet of 875/125 mg 3 times per day Note: the dose of clavulanic acid should not exceed 375 mg/day.
or slow IV7 (over at least 3 minutes) Children: 50 mg/kg once daily Adults: 1 g once daily The treatment is given by parenteral route for at least 3 days then, if the clinical condition has improved8 and oral treatment can be tolerated, switch to the oral route with amoxicillin PO as above, to complete 7 to 10 days of treatment. or ampicillin IV or IM Children: 100 mg/kg/day in 3 divided doses Adults: 3 g/day in 3 divided doses The treatment is given by parenteral route for at least 3 days then, if the clinical condition has improved8 and oral treatment can be tolerated, switch to the oral route with amoxicillin PO as above, to complete 7 to 10 days of treatment.
or
ceftriaxone IM
If the clinical condition does not improve after 48 hours with ceftriaxone + cloxacillin, consider tuberculosis. For the diagnosis, refer to the MSF handbook, Tuberculosis.
If tuberculosis is unlikely, continue with ceftriaxone + cloxacillin and add azithromycin (see Atypical pneumonia, page 72). Adjuvant therapy Fever: paracetamol PO (see Fever, page 26). Clear the airway (nasal irrigation with 0.9% sodium chloride if needed). Oxygen at the flow rate required to maintain SpO2 90% or, if pulse oxymeter is not available, minimum 1 litre/minute. Maintain adequate hydration and nutrition.
7 The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must 8 Improvement criteria include: fever reduction, diminished respiratory distress, improved O saturation, improved 2
never be administered by IV route. For IV administration, water for injection must always be used. appetite and/or activity.
9 If the only formulations of co-amoxiclav available are those with a 4:1 ratio, the dose is: 50 mg/kg/day.
71
Acute pneumonia
Follow-up in 48 to 72 hours or sooner if the patients condition deteriorates: if the patient is improving10: continue with the same antibiotic to complete treatment; if the condition is deteriorating: hospitalise and treat as severe pneumonia; If there is no improvement after 3 days of correct administration: add azithromycin (see Atypical pneumonia below).
Children: 100 mg/kg/day in 3 divided doses for 5 days Adults: 3 g/day in 3 divided doses for 5 days
Persistent pneumonia
In patients not responding to therapy, consider atypical pneumonia, tuberculosis, pneumocystosis (see page 215). First choice, azithromycin PO Children: 10 mg/kg on D1 (max. 500 mg) then, 5 mg/kg once daily from D2 to D5 Adults: 500 mg on D1 then, 250 mg once daily from D2 to D5 Bacteria responsible for atypical pneumonia are mainly Mycoplasma pneumoniae and Chlamydophila pneumoniae. If suspected, one of the following antibiotics may be used:
If not available, erythromycin PO Children: 30 to 40 mg/kg/day in 4 divided doses for 10 to 14 days Adults: 2 g/day in 4 divided doses for 10 to 14 days or doxycycline PO (except in children under 8 years and pregnant or lactating women) Children: 4 mg/kg/day (max. 200 mg/day) in 2 divided doses for 10 to 14 days Adults: 200 mg/day in 2 divided doses for 10 to 14 days
10 Improvement criteria include: fever reduction, diminished respiratory distress, improved O saturation, improved 2
72
2. Respiratory diseases
Staphylococcal pneumonia
Pneumonia due to Staphylococcus aureus affecting young children, often those in a poor general condition (malnutrition, skin lesions, etc.). Staphylococcal pneumonia is a classic complication of measles.
Clinical features
General signs: change in overall condition, pallor, high fever or hypothermia, frequently signs of shock; presence of skin lesions (point of bacterial entry), however, skin lesions may be absent. Gastrointestinal signs: nausea, vomiting, diarrhoea, painful abdominal distention. Respiratory signs: dry cough, tachypnoea, signs of distress (nasal flaring, chest indrawing). Pulmonary auscultation is often normal; sometimes dullness indicating pleural effusion. If possible, take a chest X-ray: the presence of bullae confirms the diagnosis. Pleural effusion, often unilateral, may also be seen. Treatment is urgent as patients deteriorate quickly: hospitalise. Antibiotic treatment: if staphylococcal aetiology cannot be confirmed or while waiting for confirmation, a broad spectrum antibiotic therapy is recommended: ceftriaxone IM or slow IV1 (at least 3 minutes): 50 mg/kg once daily + cloxacillin IV: 100 mg/kg/day in 4 divided doses These doses are doubled in children with HIV-infection or malnutrition or measles. After clinical improvement2, 3 days with no fever, and drain removal if any, switch to the oral route with amoxicillin/clavulanic acid PO to complete 10 to 14 days: The dose is expressed in amoxicillin: 100 mg/kg/day in 2 divided doses (if using formulations in a ratio of 8:1 or 7:1)3 Note: the dose of clavulanic acid should not exceed 12.5 mg/kg/day or 375 mg/day. In the event of large empyema: same treatment but switch to the oral route after 7 days with no fever and treat for 3 weeks. Clindamycin IV may be an alternative to cloxacillin: 30 mg/kg/day in 3 divided injections then switch to clindamycin P0 at the same dose, according to the criteria above. Fever: paracetamol PO (see page 26). Hydration by oral route or infusion or nasogastric tube depending on clinical condition (see page 69). Oxygen at the flow rate required to maintain SpO 2 90% or, if pulse oxymeter is not available, minimum 1 litre/minute. Local disinfection of skin lesions. If there is significant pleural effusion: pleural tap with drainage (for pyopneumothorax; insert 2 drains, one anterior and one posterior) or without drainage (for suppurative pleurisy, make repetitive taps with an IV catheter).
Treatment
Clinical evolution
There is a serious risk of decompensation from pneumothorax or suppurative pleurisy or pyopneumothorax. On a paediatric ward, adequate equipment for urgent pleural drainage should always be available.
1 The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must 2 Improvement criteria include: fever reduction, diminished respiratory distress, improved O saturation, improved 2
never be administered by IV route. For IV administration, water for injection must always be used. appetite and/or activity.
3 If the only formulations of co-amoxiclav available are those with a 4:1 ratio, the dose is: 50 mg/kg/day.
73
Asthma
Asthma
Asthma is a chronic inflammatory disorder of the airways associated with airway hyper-responsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness and coughing. These episodes are usually associated with airflow obstruction within the lung, often reversible, either spontaneously or with treatment.
Factors that precipitate/aggravate asthma include: allergens, infection, exercise, drugs (aspirin), tobacco, etc. In young children, most initial episodes of asthma-like symptoms are associated with a respiratory tract infection, with no symptoms between infections. Wheezing episodes usually become less frequent with time; most of these children do not develop asthma.
Asthma attack is a substantial worsening of asthma symptoms. The severity and duration of attacks are variable and unpredictable.
The severity of the asthma attack must be rapidly evaluated by the following clinical criteria. Not all signs are necessarily present. Assessment of severity in children under 2 years and adults SEVERE ATTACk MILD TO MODERATE ATTACk
Able to talk in sentences Respiratory rate (RR) Children 2-5 years 40/min Children > 5 years 30/min
LIf E THREATENINg
ATTACk
Cannot complete sentences Altered level of consciousness (drowsiness, confusion, coma) in one breath or Too breathless to talk or feed Exhaustion Silent chest Paradoxical thoracoabdominal movement
RR Pulse Children 2-5 years > 40/min Children 2-5 years 140/min Children > 5 years > 30/min Children > 5 years 125/min Adults 25/min and
No criteria of severity
Cyanosis Pulse Children 2-5 years > 140/min Children > 5 years > 125/min Collapse Adults 110/min Bradycardia in children or arrhythmia/hypotension in O2 saturation 92% adults O2 saturation < 92%
74
2. Respiratory diseases
Treatment
Treatment and follow-up depend on the severity of the attack and the patients response: Mild to moderate attack Reassure the patient; place him in a 1/2 sitting position. Administer: salbutamol (aerosol): 2 to 4 puffs every 20 to 30 minutes, up to 10 puffs if necessary during the first hour. In children, use a spacer1 to ease administration (use face mask in children under 3 years). Single puffs should be given one at a time, let the child breathe 4 to 5 times from the spacer before repeating the procedure. prednisolone PO: one dose of 1 to 2 mg/kg
If the attack is completely resolved: observe the patient for 1 hour (4 hours if he lives far from the health centre) then give outpatient treatment: salbutamol for 24 to 48 hours (2 to 4 puffs every 4 to 6 hours depending on clinical evolution) and prednisolone PO (1 to 2 mg/kg once daily) to complete 3 days of treatment.
If the attack is only partially resolved: continue with 2 to 4 puffs of salbutamol every 3 to 4 hours if the attack is mild; 6 puffs every 1 to 2 hours if the attack is moderate, until symptoms subside, then when the attack is completely resolved, proceed as above. If symptoms worsen or do not improve, treat as severe attack. Severe attack Hospitalise the patient; place him in a 1/2 sitting position.
Administer: oxygen continuously, at least 5 litres/minute or maintain the O2 saturation between 94 and 98%. salbutamol (aerosol): 2 to 4 puffs every 20 to 30 minutes, up to 10 puffs if necessary in children under 5 years, up to 20 puffs in children over 5 years and adults. Use a spacer to increase effectiveness, irrespective of age. or salbutamol (solution for nebulisation), see following page. prednisolone PO: one dose of 1 to 2 mg/kg In the case of vomiting, use hydrocortisone IV every 6 hours (children: 5 mg/kg/injection, adults: 100 mg/injection) until the patient can tolerate oral prednisolone. If the attack is completely resolved, observe the patient for at least 4 hours. Continue the treatment with salbutamol for 24 to 48 hours (2 to 4 puffs every 4 hours) and prednisolone PO (1 to 2 mg/kg once daily) to complete 3 days of treatment. Reassess after 10 days: consider long-term treatment if the asthma attacks have been occurring for several months. If the patient is already receiving long-term treatment, reassess the severity of the asthma (see table, page 77) and review compliance and correct use of medication and adjust treatment if necessary. If symptoms worsen or do not improve, see life-threatening attack.
1 If a conventional spacer is not available, use a 500 ml plastic bottle: insert the mouthpiece of the inhaler into a hole
made in the bottom of the bottle (the seal should be as tight as possible). The child breathes from the mouth of the bottle in the same way as he would with a spacer. The use of a plastic cup instead of a spacer is not recommended (ineffective). 75
Asthma
For patients who do not respond rapidly to nebulised salbutamol: In adults, administer a single dose of magnesium sulfate (infusion of 1 to 2 g in 0.9% sodium chloride over 20 minutes). In children, use continuous nebulisation rather than intermittent nebulisation.
Administer: oxygen continuously, at least 5 litres/minute or maintain the O2 saturation between 94 and 98%. salbutamol (solution for nebulisation): Children under 5 years or 15 kg: 2.5 mg/nebulisation, to be repeated every 20 to 30 minutes if necessary until clinical improvement is achieved; switch to salbutamol aerosol (using a spacer) as soon as possible. Children over 5 years and adults: 2.5 to 5 mg/nebulisation, to be repeated every 20 to 30 minutes if necessary until clinical improvement is achieved; switch to salbutamol aerosol as soon as possible. Salbutamol must be administered via an oxygen-driven nebuliser. hydrocortisone IV every 6 hours (children: 5 mg/kg/injection, adults: 100 mg/injection).
Notes: In pregnant women, treatment is the same as for adults. In mild or moderate asthma attacks, administering oxygen reduces the risk of foetal hypoxia. For all patients, irrespective of the severity of the asthma attack, look for underlying lung infection and treat accordingly.
Chronic asthma
Clinical features
Asthma should be suspected in patients with episodic respiratory symptoms (wheezing, chest tightness, shortness of breath and/or cough) of variable frequency, severity and duration, disturbing sleep, and causing the patient to sit up to breathe. These symptoms may appear during or after exercise. Chest auscultation may be normal or demonstrate diffuse sibilant wheezes.
Atopic disorders or a personal or family history of atopy (eczema, allergic rhinitis/conjunctivitis) or a family history of asthma increases probability of asthma but their absence does not exclude asthma. Patients with typical symptoms of asthma and a history of disease that is characteristic of asthma should be considered as having asthma after exclusion of other diagnoses. The assessment of the frequency of daytime and nigthtime symptoms and limitations of physical activity determines whether asthma is intermittent or persistent.
76
2. Respiratory diseases
Treatment
Only patients with persistent asthma need long-term treatment. The mainstay of treatment is inhaled corticosteroids. Treatment is started at the step most appropriate to initial severity then, re-evaluated and adjusted according to clinical response. It aims to abolish symptoms with the lowest possible dose of inhaled corticosteroids. An intervening severe exacerbation or loss of control necessitates reassessment to reevaluate treatment. Long-term treatment does not mean treatment for life. Asthma attacks may occur over months or years, with intervening asymptomatic intervals when long-term treatment is not required. Long-term treatment of asthma according to severity Categories
Intermittent asthma Intermittent symptoms (< once/week) Night time symptoms < twice/month Normal physical activity Mild persistent asthma Symptoms > once/week, but < once/day Night time symptoms > twice/month Symptoms may affect activity Moderate persistent asthma Daily symptoms Symptoms affect activity Night time symptoms > once/week Daily use of salbutamol No long term treatment Inhaled salbutamol when symptomatic Continuous treatment with inhaled beclometasone + Inhaled salbutamol when symptomatic Continuous treatment with inhaled beclometasone + Inhaled salbutamol (1 puff 4 times/day) Continuous treatment with inhaled beclometasone + Inhaled salbutamol (1-2 puff/s 4 to 6 times/day)
Treatment
Inhaled corticosteroid treatment: beclometasone dose varies according to the severity of asthma. Find the minimum dose necessary to both control the symptoms and avoid local and systemic adverse effects: Children: 50 to 100 micrograms twice daily depending on the severity. Increase to 200 micrograms twice daily if the symptoms are not controlled. In patients with severe chronic asthma the dosage may be as high as 800 micrograms/day. Adults: start with 250 to 500 micrograms twice daily depending on to the severity. If a total dosage of 1000 micrograms/day (in 2 to 4 divided doses) is ineffective, the dosage may be increased to 1500 micrograms/day, but the benefits are limited. The number of puffs of beclometasone depends on its concentration in the inhaled aerosol: 50, 100 or 250 micrograms/puff. To avoid dosing errors, use only inhalers of 50 or 100 micrograms/puff for children. Reserve inhalers of 250 micrograms/puff for adults.
Severe persistent asthma Daily symptoms Frequent night time symptoms Physical activity limited by symptoms
77
Asthma
Do not restrict exercise. If exercise is a trigger for asthma attacks, administer 1 or 2 puffs of salbutamol 10 minutes beforehand. In pregnant women, poorly controlled asthma increases the risk of pre-eclampsia, eclampsia, haemorrhage, in utero growth retardation, premature delivery, neonatal hypoxia and perinatal mortality. Long-term treatment remains inhaled salbutamol and beclometasone at the usual dosage for adults. Whenever possible, avoid oral corticosteroids. If symptoms are not well controlled during a period of at least 3 months, check the inhalation technique and adherence before changing to a stronger treatment.
If symptoms are well controlled for a period of at least 3 months (the patient is asymptomatic or the asthma has become intermittent): try a step-wise reduction in medication, finally discontinuing treatment, if it seems possible. Provide patients with a salbutamol inhaler for any possible attacks. Evaluate after 2 weeks. If the results are satisfactory, continue for 3 months and then re-evaluate. If the patient has redeveloped chronic asthma, restart long-term treatment, adjusting doses, as required.
78
2. Respiratory diseases
Pulmonary tuberculosis
Pulmonary tuberculosis is a bacterial infection due to Mycobacterium tuberculosis, spread by airborne route. After contamination, M. tuberculosis multiplies slowly in the lungs: this represents the primary infection. In immunocompetent patients, the pulmonary lesion heals in 90% of cases, but in 10%, patients develop active tuberculosis. Tuberculosis may also be extrapulmonary: tuberculous meningitis, disseminated tuberculosis, lymph node tuberculosis, spinal tuberculosis, etc.
Patients with HIV infection have an increased risk of developing active tuberculosis. Tuberculosis is the opportunistic disease that most commonly reveals AIDS. In certain countries, up to 70% of patients with tuberculosis are co-infected with HIV.
Clinical features
Prolonged cough (> two weeks), sputum production, chest pain, weight loss, anorexia, fatigue, moderate fever, and night sweats. The most characteristic sign is haemoptysis (presence of blood in sputum), however it is not always present and haemoptysis is not always due to tuberculosis. If sputum is smear-negative, consider pulmonary distomatosis (page 149), melioidosis (Southeast Asia), profound mycosis or bronchial carcinoma. In an endemic area, the diagnosis of tuberculosis is to be considered, in practice, for all patients consulting for respiratory symptoms for over two weeks who do not respond to non-specific antibacterial treatment.
Diagnosis
Sputum smear microscopy; culture Chest X-rays are useful for the diagnosis of smear negative tuberculosis and tuberculosis in children. The treatment is a combination of several of the following antituberculous drugs [isoniazid (H), rifampicin (R), pyrazinamide (Z), ethambutol (E), streptomycin (S)]. The regimen is standardised and organized into 2 phases (initial phase and continuation phase). The treatment of drug-sensitive tuberculosis lasts a minimum of 6 months.
Treatment
It takes significant investment to cure a TB patient, both from the patient and the medical team. Only uninterrupted treatment for several months may lead to cure and prevent the development of resistance, which complicates later treatment. It is essential that the patient understands the importance of treatment adherence and that he has access to correct case management until treatment is completed.
79
Pulmonary tuberculosis
Prevention
When BCG is correctly carried out, it confers protection that is not insignificant (probably over 50%). It has been proven that BCG protects against severe forms of the disease, in particular tuberculous meningitis and miliary tuberculosis. BCG vaccination does not diminish transmission of tuberculosis. For more information on the diagnosis, treatment and prevention of tuberculosis, and on the follow-up of tuberculosis patients, refer to the MSF handbook, Tuberculosis.
80
CHAPTER 3
Gastrointestinal disorders
Acute diarrhoea Shigellosis Amoebiasis Disorders of the stomach and duodenum Stomatitis 83 86 88 89 92
3. Gastrointestinal disorders
Acute diarrhoea
Acute diarrhoea is defined as at least 3 liquid stools per day for less than 2 weeks. There are 2 clinical types of acute diarrhoea: Simple diarrhoea without blood, caused by viruses in 60% of cases (rotavirus, enterovirus), bacteria (Vibrio cholerae, enterotoxigenic Escherichia coli, non-typhi Salmonella, Yersinia enterocolitica) or parasites (giardiasis). Diseases, such as malaria, acute otitis media, upper and lower respiratory tract infections, etc. can be accompanied by this type of diarrhoea. Dysentery or bloody diarrhoea , caused by bacteria ( Shigella in 50% of cases, Campylobacter jejuni , enteroinvasive or enterohaemorrhagic Escherichia coli , Salmonella) or parasites (intestinal amoebiasis). The high mortality rate from diarrhoeal diseases, even benign, is due to acute dehydration and malnutrition. This can be prevented by adequate rehydration and nutrition. First assess for signs of dehydration. See Assessment of diarrhoeal patients for dehydration, WHO, page 305. Then look for other signs: profuse watery diarrhoea (cholera, enterotoxigenic E. coli), repeated vomiting (cholera), fever (salmonella, viral diarrhoea), presence of red blood in stools: see Shigellosis, page 86 and Amoebiasis, page 88. In a patient over 5 years with severe and rapid onset of dehydration, suspect cholera.
Infectious diarrhoeas are transmitted by direct (dirty hands) or indirect (ingestion of contaminated water or food) contact.
Clinical features
Treatment
General principles: Prevent or treat dehydration: rehydration consists of prompt replacement of fluid and electrolyte losses as required, until the diarrhoea stops. Administer zinc sulfate to children under 5 years. Prevent malnutrition. Do not systematically administer antimicrobials: only certain diarrhoeas require antibiotics (see antimicrobial treatment, following page). Do not administer anti-diarrhoeal drugs or antiemetics. Treat the underlying condition if any (malaria, otitis, respiratory infection, etc.).
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Acute diarrhoea
Severe dehydration (at hospital level) Follow Treatment plan C to treat severe dehydration quickly, WHO, page 321. In the event of hypovolaemic shock or if there is no improvement after one hour: increase the infusion rate. Check for signs of fluid overload: palpebral oedema is the first sign of overhydration. Stop rehydration until oedema disappear. If there are signs of acute pulmonary oedema (laryngeal crackles, dyspnoea and increased respiration rate, coughing with or without frothy sputum, distress, bilateral lung crepitations, tachycardia etc.), administer IV furosemide immediately and repeat after one to 2 hours if required: Children: 1 mg/kg/injection Adults: 40 mg/injection Special situations Cholera In the event of severe dehydration, an adult may require up to 10 to 15 litres of Ringer Lactate (RL) on the first day. RL potassium content is low. There is a risk of symptomatic hypokalaemia in patients exclusively rehydrated by IV route. Thus, start oral rehydration solution (SRO) as soon as possible in patients under infusion.
Moderate dehydration (at dispensary level) Follow Treatment plan B to treat dehydration, WHO, page 308.
Oral rehydration and severe malnutrition Use standard rehydration salts (SRO) in cholera patients only. In all other cases, use ReSoMal (see Severe acute malnutrition, page 40). Zinc sulfate is given in combination with oral rehydration solution in order to reduce the duration and severity of diarrhoea, as well as to prevent further occurrences in the 2 to 3 months after treatment: zinc sulfate PO Children under 6 months: 10 mg once daily (1/2 tablet once daily) for 10 days Children from 6 months to 5 years: 20 mg once daily (1 tablet once daily) for 10 days Place the half-tablet or full tablet in a teaspoon, add a bit of water to dissolve it, and give the entire spoonful to the child. Do not administer this treatment if the child receives ready-to-use therapeutic food (RUTF) which already contains zinc.
Prevention of malnutrition
3. Gastrointestinal disorders
Antimicrobial treatment
Diarrhoea without blood Most acute diarrhoeas are caused by viruses unresponsive to antimicrobials. Antimicrobials can be beneficial in the event of cholera or giardiasis.
Cholera: the most important part of treatment is rehydration. In the absence of resistance (perform antibiotic-sensitivity testing), antibiotic treatment shortens the duration of diarrhoea: doxycycline PO Children: 4 mg/kg as a single dose Adults: 300 mg as a single dose or azithromycin PO Children: 20 mg/kg as a single dose Adults: 1 g as a single dose Giardiasis: tinidazole or metronidazole, see page 147. Bloody diarrhoea (dysentery) Note: doxycycline is usually contraindicated in pregnant women and children under 8 years. However, for treating cholera, the administration of a single dose should not provoke any adverse effects. Check national recommendations.
Shigellosis is the most frequent cause of dysentery (amoebic dysentery is much less common). If there is no laboratory diagnosis to confirm the presence of amoebae, first line treatment is for shigellosis (see page 86). Amoebiasis: antiparasitic treatment only if motile E. histolytica amoebae are found in stools or if a correct shigellosis treatment has been ineffective (see page 88).
Prevention
Breastfeeding reduces infant morbidity and mortality from diarrhoea and the severity of diarrhoea episodes.
When the child is weaned preparation and storage of food are associated with the risk of contamination by faecal micro-organisms: discourage bottle-feeding; food must be cooked well; milk or porridge must never be stored at room temperature.
Access to sufficient amounts of clean water and personal hygiene (washing hands with soap and water before food preparation and before eating, after defecation etc.) are effective methods of reducing the spread of diarrhoea.
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Shigellosis
Shigellosis
There are 4 serogroups of shigella: S. flexneri, S. boydii, S. sonnei and S. dysenteriae. Shigella dysenteriae type 1 (Sd1) is the only strain that causes large scale epidemics. Of the 4 serogroups it has the highest case fatality rate (up to 10%).
Ciprofloxacin is currently the only effective treatment for shigellosis. It is therefore essential to prevent the development of resistances.
Clinical features
Bloody diarrhoea with or without fever, abdominal pain and tenesmus, which is often intense. Patients with at least one of the following criteria have an increased risk of death: Signs of serious illness: fever > 38.5C malnutrition (< 80% of the median) severe dehydration confusion, seizures or coma Age groups at risk: children under 5 years adults over 50 years
Treatment
For pain:
Antibiotic treatment: ciprofloxacin PO is the first line treatment Children: 30 mg/kg/day in 2 divided doses for 3 days Adults: 1 g/day in 2 divided doses for 3 days in pregnant women, ciprofloxacin is contra-indicated in principle, use ceftriaxone IM: 1 g once daily for 3 to 5 days Amoxicillin is ineffective in vivo. The use of nalidixic acid favours the development of ciprofloxacin resistance.
hyoscine butylbromide PO
Supportive therapy: nutrition: all patients with dysentery should receive nutritional supplements 2500 kcal/day during hospitalisation 1000 kcal/day as outpatients Children already in nutritional centres should be isolated. rehydration: systematic administration of ORS (follow the WHO protocols, pages 316 to 321).
86
Children from 6 to 12 years: 10 mg, to be repeated every 8 hours if necessary Adults: 10 to 20 mg, to be repeated every 8 hours if necessary All opioid analgesics are contra-indicated as they slow peristalsis.
3. Gastrointestinal disorders
Complications of shigellosis due to Sd1: septicaemia: see antibiotic treatment of septic shock (page 20) acute abdomen: see antibiotic treatment of septic shock (page 20) and laparotomy seizures: diazepam (page 23) and fluid restriction moderate to severe haemolytic uraemic syndrome, may require transfusion and/or haemodialysis.
Antibiotic resistance develops rapidly (sometimes during the course of an epidemic). After confirming the causal agent, antimicrobial susceptibility should be monitored monthly by culture and sensitivity tests.
Patients presenting with signs of serious illness or with risk factors are hospitalised for the duration of treatment and are monitored daily (clinically and for compliance). Patients with neither signs of serious illness nor risk factors are treated as outpatients. Organise home visits for daily monitoring (clinically and for compliance); hospitalise if the patient develops signs of serious illness. Hygiene measures: isolate patients as for cholera, individual and collective hygiene. Shigellosis is an extremely contagious disease (the ingestion of 10 bacteria is infective). Note: over the past few years, Sd1 epidemics of smaller scale and with lower case fatality rates (less than 1%) have been observed.
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Amoebiasis
Amoebiasis
Amoebiasis is a parasitic infection due to the intestinal protozoa Entamoeba histolytica. Transmission is faecal-oral, by ingestion of amoebic cysts from food or water contaminated with faeces. Usually, ingested cysts release non-pathogenic amoebae and 90% of carriers are asymptomatic. In 10% of infected patients, pathogenic amoebae penetrate the mucous of the colon: this is the intestinal amoebiasis (amoebic dysentery). The clinical picture is similar to that of shigellosis, which is the principal cause of dysentery. Occasionally, the pathogenic amoebae migrate via the blood stream and form peripheral abscesses. Amoebic liver abscess is the most common form of extra-intestinal amoebiasis.
Clinical features
Amoebic dysentery diarrhoea containing red blood and mucus abdominal pain, tenesmus no fever or moderate fever possibly signs of dehydration
Amoebic liver abscess painful hepatomegaly; mild jaundice may be present anorexia, weight loss, nausea, vomiting intermittent fever, sweating, chills; change in overall condition
Laboratory
Amoebic dysentery: identification of mobile trophozoites (E. histolytica histolytica) in fresh stool samples Amoebic liver abscess: indirect haemoagglutination and ELISA
Treatment
Amoebic dysentery The presence of cysts alone should not lead to the treatment of amoebiasis. Amoebiasis confirmed with a parasitological stool examination: tinidazole PO Children: 50 mg/kg once daily for 3 days (without exceeding 2 g/day) Adults: 2 g once daily for 3 days or metronidazole PO Children: 45 mg/kg/day in 3 divided doses for 5 days Adults: 1.5 g/day in 3 divided doses for 5 days If there is no laboratory, first line treatment for dysentery is for shigellosis (see page 86). Treat for amoebiasis if correct treatment for shigellosis has been ineffective. Oral rehydration salts (ORS) if there is risk of, or if there are signs of dehydration (follow the WHO protocols, pages 316 to 321). Amoebic liver abscess tinidazole PO: same treatment as for amoebic dysentery for 5 days metronidazole PO: same treatment as for dysentery for 5 to 10 days
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3. Gastrointestinal disorders
Treatment
For an isolated episode: identify patients taking NSAID or acetylsalicylic acid; stop treatment encourage patients to avoid alcohol and tobacco use omeprazole PO: 20 mg once daily in the morning for 7 to 10 days or, if not available, cimetidine PO: 800 mg once daily at bedtime for 7 to 10 days If the patient has frequent recurrences, unrelated to NSAID use, that require repeated treatment with antiulcer drugs: see eradication of Helicobacter pylori, next page.
1 Aluminium hydroxide may decrease absorption of drugs taken at the same time, leave an interval of at least
89
If the haemorrhage continues (haematemesis) and/or if the haemodynamic state deteriorates (pulse increases, BP drops): Intensive care and transfusion according to the severity of the bleeding (see Haemorrhagic shock, page 19). Emergency surgical intervention. Most peptic ulcers are caused by Helicobacter pylori infection. If a diagnosis of ulcer is probable, and the patient has frequent attacks requiring repeated treatment with antiulcer drugs or, in cases of complicated ulcers (perforation or gastrointestinal bleeding) treatment to eradicate H. pylori should be considered to prevent relapses. Once the acute phase has passed, prescribe one of the following treatments:
metronidazole PO 2
1 g/day in 2 divided doses + amoxicillin PO 2 g/day in 2 divided doses + omeprazole PO 40 mg/day in 2 divided doses
1 g/day in 2 divided doses + amoxicillin PO 2 g/day in 2 divided doses + bismuth subcitrate PO 480 mg/day in 4 divided doses
metronidazole PO 2
1 g/day in 2 divided doses + amoxicillin PO 2 g/day in 2 divided doses + cimetidine PO 1600 mg/day in 2 divided doses
metronidazole PO 2
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3. Gastrointestinal disorders
Notes: Acetylsalicylic acid (aspirin) and NSAID (indometacin, ibuprofen, diclofenac etc) are contra-indicated in patients suffering from or with a history of ulcers. Omeprazole is as effective PO as IV.
Dyspepsia
Clinical features
Epigastric pain or discomfort following meals, often accompanied by bloating, sensation of fullness and nausea. Dyspepsia is most commonly functional, linked with stress and not linked to the quantity of gastric acid (antiacids and antiulcer drugs are ineffective). Resolution is usually spontaneous.
Treatment
In adults:
Note: consider and treat possible intestinal parasites (taeniasis, ascariasis, ancylostomiasis, giardiasis, amoebiasis).
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Stomatitis
Stomatitis
Stomatitis is an inflammation of the mucous membranes of the mouth caused by a fungal, viral or bacterial infection, a vitamin deficiency, an injury, etc. Prolonged or painful stomatitis may contribute to dehydration or may cause loss of appetite with denutrition, particularly in children. In infants, examine routinely the mouth in the event of breast refusal or difficulties in sucking. In all cases: Maintain adequate hydration and feeding; offer foods that will not irritate the mucosa (soft, non-acidic). Use a nasogastric tube for a few days if pain is preventing the patient from eating. Keep the mouth clean to prevent complications and recurrence.
Infection due to Candida albicans, common in infants, immunocompromised or diabetic patients. Other risk factors include treatment with oral antibiotics or high-dose inhaled corticosteroids.
Clinical features
White patches on the tongue, inside the cheeks, that may spread to the pharynx.
In patients with frequent recurrences or extensive forms invading the esophagus (swallowing difficulty and pain), consider HIV infection. (to be taken between meals): 400 000 IU/day, i.e. 1 lozenge to be sucked or 1 ml of the oral suspension (100 000 IU) 4 times/day for 7 days. The oral suspension should be swilled around the oral cavity and swallowed, or, in young children, applied to the tongue and the inside of each cheek. Show the mother how to treat since in most cases, candidiasis will be treated at home.
nystatin
Treatment
Infection due to the herpes simplex virus. Primary infection typically occurs in children aged 6 months-5 years and may cause acute gingivostomatitis, sometimes severe. After primary infection, the virus remains in the body and causes in some individuals periodic recurrences which are usually benign (herpes labialis).
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Oral herpes
3. Gastrointestinal disorders
Clinical features
Primary herpetic gingivostomatitis: multiple vesicles on the oral mucosa and lips which rupture to form painful, yellowish, at times extensive ulcers. Local lesions are usually associated with general malaise, regional lymphadenopathy and fever. Recurrent herpes labialis: clusters of vesicles at the junction between the lip and the skin. In patients with frequent recurrences or extensive forms, consider HIV infection (see page 214).
Treatment
Treat pain: paracetamol or ibuprofen PO. In the event of severe lesions, inability to drink and significant pain: admit the child to hospital (high risk of dehydration); if the child presents within the first 96 hours of symptoms onset, aciclovir PO for 5 to 7 days: Children under 2 years: 200 mg 5 times per day Children over 2 years: 400 mg 5 times per day In the event of secondary bacterial infection: amoxicillin PO 7 days. In immunocompromised patients: see page 214. Recurrent herpes labialis Spontaneous resolution within 7 to 10 days. An antiseptic (chlorhexidine or polyvidone iodine) may be applied; paracetamol PO if necessary. Both forms of herpes are contagious: do not touch lesions (or wash hands afterwards); avoid oral contact. Primary herpetic gingivostomatitis
For scarlet fever (strawberry tongue associated with a skin rash): phenoxymethylpenicillin (pencillin V) PO for 10 days Children under 1 year: 250 mg/day in 2 divided doses Children from 1 to 5 years: 500 mg/day in 2 divided doses Children from 6 to 12 years: 1 g/day in 2 divided doses Adults: 2 g/day in 2 divided doses
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Stomatitis
Treatment
The treatment is continued until symptoms improve (1 to 2 weeks), then a preventive treatment (children and adults: 25 to 50 mg/day) is given as long as the situation requires.
Other vitamin deficiencies may provoke mouth lesions: angular stomatitis of the lips and glossitis from vitamin B2 (riboflavin), niacin (see Pellagra, page 118) or vitamin B6 (pyridoxine) deficiencies. Iron deficiency may also provoke angular stomatitis (see Anaemia, page 37). Give the corresponding vitamins at curative doses. Multivitamins are insufficient to treat true vitamin deficiencies.
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CHAPTER 4
Skin diseases
Dermatology Scabies Lice (pediculosis) 97 101 103 105 109 113 116 117 111 98
Superficial fungal infections Bacterial skin infections Cutaneous anthrax Treponematoses Leprosy
4. Skin diseases
Dermatology
Skin diseases, particularly infectious skin diseases, are very common. They must be treated individually or collectively, but must also be considered as indicators of the sanitary condition of a population. A high prevalence of infectious skin diseases may reflect a problem of insufficient water quantity and lack of hygiene in a population.
Dermatological examination
Look at the distribution of the lesions over the body; observe their arrangement: isolated, clustered, linear, annular (in a ring). Ask if the lesions are itchy. Look for a possible cause: insect bites; scabies, lice, other parasitic skin infections; contact with plants, animals, jewellery, detergents, etc. Ask about any ongoing treatment: topical, oral or parenteral. Look for local or regional signs (secondary infection, lymphangitis, adenopathy, erysipelas) and/or systemic signs (fever, septicaemia, distant infectious focus). Check tetanus vaccination status.
Observe the type of lesion: Macule: flat, non palpable lesion that is different in colour than the surrounding skin Papule: small (< 1 cm) slightly elevated, circumscribed, solid lesion Vesicle (< 1 cm), bulla (> 1 cm): clear fluid-filled blisters Pustule: vesicle containing pus Nodule: firm, elevated palpable lesion (> 1 cm) that extend into the dermis or subcutaneous tissue. Erosion: loss of the epidermis that heals without leaving a scar Excoriation: erosion caused by scratching Ulcer: loss of the epidermis and at least part of the dermis that leaves a scar Scale: flake of epidermis that detaches from the skin surface Crust: dried serum, blood, or pus on the skin surface Atrophy: thinning of the skin Lichenification: thickening of the skin with accentuation of normal skin markings
Consider the sanitary condition of the family, particularly for contagious skin diseases (scabies, scalp ringworm, lice).
Patients with skin disease often present late. At this stage, primary lesions and specific signs may be masked by secondary infection. In these cases, it is necessary to reexamine the patient, after treating the secondary infection, in order to identify and treat the underlying skin disease.
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Scabies
Scabies
Scabies is a cutaneous parasitosis due to the presence of the mite Sarcoptes scabiei hominis within the epidermis. It exists in two forms: ordinary scabies, relatively benign and moderately contagious; and crusted scabies, favoured by immune deficiency, extremely contagious and refractory to conventional treatment. Person to person transmission takes place chiefly through direct skin contact, and sometimes by indirect contact (sharing clothing, bedding). The challenge in management is that it must include simultaneous treatment of both the patient and close contacts, and at the same time, decontamination of clothing and bedding of all persons undergoing treatment, in order to break the transmission cycle.
Vesicular eruption; often involving palms and soles, back, face, and limbs. Secondary infection or eczematisation is frequent. Isolated scabies nodules in the axillae may be the only manifestation. Examination of the mothers hands may support the diagnosis.
Thick, scaly, erythematous plaques, generalised or localised, resembling psoriasis, with or without itching (50% of cases). Delay in diagnosis may lead to a scabies epidemic.
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4. Skin diseases
Ordinary scabies
Topical treatment Topical scabicides are applied over the entire body (including the scalp, post-auricular areas, umbilicus, palms and soles), avoiding mucous membranes and face, and the breasts in breastfeeding women. Particular attention should be paid to common infestation sites. The recommended contact time should not be shortened or exceeded; the patient must not wash his hands while the product is in use (or the product should be reapplied if the hands are washed). In infants, the hands must be wrapped to prevent accidental ingestion of the product. Topical scabicides should not be applied to broken or inflamed skin. Treatment of secondary bacterial infection, if present, should be initiated 24 to 48 hours before use of topical scabicides (see Impetigo, page 105).
The preferred treatment is 5% permethrin (lotion or cream): Child > 2 months and adult: one application, with a contact time of 8 hours, then rinse off. Permethrin is easier to use (no dilution required), and preferred over benzyl benzoate in children, and pregnant/lactating women. One application may be sufficient, but a second application 7 days later reduces the risk of treatment failure. or, if not available, benzyl benzoate 25% lotion:
Children < 2 years Dilution Contact time 1 part 25% lotion + 3 parts water Children 2-12 years 1 part 25% lotion + 1 part water Children > 12 years and adults Use undiluted 25% lotion 24 hours, then rinse off
A second application of benzyl benzoate (e.g. after 24 hours, with a rinse between the 2 applications; or two successive applications, 10 minutes apart, when the first application has dried, with a rinse after 24 hours) reduces the risk of treatment failure. Second applications are not recommended in pregnant women and children < 2 years. Treatment with ivermectin PO (200 micrograms as a single dose) is an alternative: it is more practical than topical treatment (e.g. in the case of an epidemic or for treating contacts) and can be started right away in the case of secondary infection. A single dose may be sufficient; a second dose 7 days later reduces the risk of treatment failure.
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Oral treatment
Scabies
Ivermectin is not recommended for children < 15 kg or pregnant women (safety not established)1. Administration of ivermectin to patients with loiasis carries a risk of severe neurological complications when significant Loa loa microfilaraemia is present (see Filariasis, page 157)2.
Weight Ivermectin 3 mg tab Ivermectin 6 mg tab 15 to 24 kg 1 tab tab 25 to 35 kg 2 tab 1 tab 36 to 50 kg 11/2 tab 3 tab 51 to 65 kg 4 tab 2 tab
Treatment effectiveness is judged on clinical grounds. Itching may persist for 1 to 3 weeks after elimination of the parasite. Persistence of typical burrows beyond 3 weeks should lead to suspicion of treatment failure (insufficient treatment, e.g. the scalp was not included in topical treatment or the patient washed his hands during the treatment period), or early re-infestation (contacts and environment not treated). In these cases, patient and contacts should be retreated. Persistent itching may be due to another condition, initially masked by scabies.
1/2
Crusted scabies
Treatment combines simultaneous administration of oral ivermectin and topical scabicide at regular intervals, e.g. every week for 2 to 3 weeks or more, according to severity and clinical response. Crusts should be softened (salicylic acid ointment) and removed before applying local treatment (otherwise, local treatment is ineffective). As exfoliated skin scales may spread the parasite, the patient should be isolated during the treatment, staff should use protection (gloves, gowns and hand washing after contact), and environment (bedding, floors and surfaces) should be decontaminated.
1 Treatment with ivermectin in these patients is reserved for severe cases for which no alternative exists (see
2 In areas where loiasis is endemic, certain precautions are recommended before administering ivermectin: e.g.
crusted scabies).
measure the Loa loa microfilaraemia, if possible, or ensure that the patient has no history of loiasis (migration of an adult worm under the conjunctiva or transient Calabar swellings), nor history of severe adverse reactions following a previous treatment with ivermectin, or if in doubt, use topical treatment in preference to oral.
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4. Skin diseases
Lice (pediculosis)
Pediculosis is a benign contagious parasitic infection due to 3 species of lice specific to humans: head lice, body lice and pubic lice. Transmission from person to person occurs through direct or indirect contact. Body lice are potential vectors of relapsing fever (page 182), typhus (page 185) and trench fever.
Clinical features
Head lice mainly affect children: itching and scratch marks (nape of neck and around the ears), which may become secondarily infected (impetigo) in prolonged infestation; presence of live lice and/or live (shiny, grey) nits attached to the hair shaft within 5 mm of the scalp. Body lice mainly affect populations living under poor conditions (refugees, prisoners, the homeless): itching and scratch marks (back, belt line and armpits), often inflamed and infected; presence of lice and nits in the clothing (parasites are not found on the body). Pubic lice are considered to be a sexually transmitted infection (STI): itching and scratch marks (pubic and perianal area), but other hairy areas may also be affected (armpits, thighs, eyelashes); lice and nits at the base of the hair shaft, rarely visible. Examine contacts; check for associated systemic infection (body lice) or STI (pubic lice).
Treatment
Apply to dry hair 1% permethrin lotion (leave on for 10 min) or 0.5% malathion lotion (leave on for 12 hours; 8 hours in children 6 months-2 years). Do not reduce or exceed the recommended duration of treatment. Rinse thoroughly. Decontaminate combs, headwear and bedding (wash 60C/30 min, iron or dry in the sun or, if not feasible, seal in a plastic bag for 2 weeks). Treat those contacts with lice and/or live nits, not those with dead nits alone (dull, white, > 1 cm from scalp) as above. It is recommended to repeat the application after 10 days. Body lice For mass treatment (outbreak): apply 30 to 60 g (2 to 4 heaped soup spoons) of 0.5% permethrin powder to the inside of the clothes and underclothes in contact with the skin (front and back, neck and waistline, sleeves and socks) in a fully clothed patient, then rub in the powder by hand. Leave for 12 to 24 hours. Treat other clothing (including headwear) and bedding in a plastic bag with 0.5% permethrin powder. Repeat in 8 to 10 days if the infestation persists.
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Head lice
Lice (pediculosis)
For individual treatment: disinfection of clothing and bedding as above or as for head lice. Pubic lice Shave and/or apply 1% permethrin lotion to hairy areas (as for head lice). Treat the partner at the same time. Decontaminate clothing and bedding (as for head lice). Repeat the application after 7 days. Treatment of secondary bacterial infection, if present, should begin 24 to 48 hours before local antiparasitic treatment (see Impetigo, page 105); local treatment is applied later when tolerated.
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4. Skin diseases
If diaper dermatitis is severe and persistent despite these measures, consider an intestinal infection (nystatin PO: 400 000 IU/day in 4 divided doses for 20 days). Other candidiasis Candidiasis of skin folds: miconazole 2% cream, twice daily for 2 to 4 weeks Oral candidiasis: see Stomatitis, page 92. Vulvovaginal candidiasis: see Abnormal vaginal discharge, page 233.
Dermatophytes cause various clinical lesions, depending on the anatomic site involved: scalp, glabrous (hairless) skin, folds or nails. See following page.
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104
Dermatophytoses
Treatment
Anatomic site1
Clinical features
Shave or cut hair short on and around the lesions. Common in children. Local treatment: 2 times/day, clean with soap and water, dry and apply miconazole 2% Depending on the species: One or more round, scaly, erythematous cream or Whitfields ointment for 2 weeks or longer if necessary. Administer systemic treatment as local treatment alone does not cure scalp ringworm: plaques with the ends of broken hairs. griseofulvin PO for 6 weeks (up to 8 to 12 weeks) Inflammation, suppuration, crusting and Children 12 years: 10 to 20 mg/kg/day in 1 or 2 divided doses (max. 500 mg/d) peripheral lymphadenopathy (kerion). Children > 12 years and adults: 500 mg to 1 g/day in 1 or 2 divided doses Permanent hair loss (favus). or itraconazole PO Some scalp ringworms are contagious: Children: 3 to 5 mg/kg once daily for 4 weeks (max. 200 mg/d) simultaneously examine (and treat) symptomatic Adults: 200 mg once daily for 2 to 4 weeks Suppurative lesions: treat superinfection (see Impetigo, page 105) before applying local contacts. antifungal treatment. For painful kerion: paracetamol PO. In pregnant lactating/breastfeeding women: oral antifungals are contraindicated. Apply a topical treatment (miconazole 2% cream or Whitfields ointment) to limit the spread of infection until it is possible to treat orally.
1 Dermatophytosis may affect the nails (Tinea unguium, onychomycosis). Treatment is prolonged (12 to 18 months with griseofulvin) thus, in practice, difficult.
Topical treatment as above. If oozing lesions, use miconazole 2% cream only (do not use Interdigital spaces (Tinea pedis): Pruritus, fissure and whitish scales in the 3rd Whitfields ointment). and/or 4th interdigital spaces2. Groin (Tinea cruris): Circumscribed, pruritic, erythematous plaque, with a pale centre surrounded by vesiculopustules, extending outward from the groin.
Erythematous, scaly, pruritic macule with a For non widespread, localised tinea: well-demarcated, raised, vesicular border and Local treatment: 2 times/day, clean with soap and water, dry and apply miconazole 2% cream or Whitfields ointment for 2 to 4 weeks or for 2 weeks after clinical resolution. central healing. Reserve oral antifungals for particularly extensive lesions: griseofulvin PO for 4 to 6 weeks or itraconazole for 15 days.
2 In candidal intertrigo, lesions are usually located in the 1st and 2nd interdigital spaces.
4. Skin diseases
Clinical features
Classic form: flaccid vesicule on erythematous skin which becomes pustular and forms a yellowish crust. Different stages of the infection may be present simultaneously. The lesion does not leave a scar. The most common sites of infection are around the nose and mouth, on the limbs or on the scalp. There is no fever. Bullous impetigo: large flaccid bullae and erosions of the skin in the ano-genital region in newborns and infants. Ecthyma: an ulcerative form of impetigo that leaves scars. Lesions usually occur on the lower limbs. This form is most common in the immunocompromised, diabetics and alcoholics. Rare complications: abscess, pyodermitis, lymphangitis, osteomyelitis, septicaemia; systematically look for signs of acute glomerulonephritis.
Treatment
Localised impetigo (less than 3 lesions on the same region of the body): Clean with soap and water 2 times/day and dry. Soften crusts if present by applying vaseline and gently remove them. Keep dry (do not cover with an occlusive dressing; if on the buttocks of children, leave uncovered, etc.). Keep fingernails short. Extensive impetigo (more than 3 lesions or impetigo on more than one region of the body), bullous impetigo, ecthyma, abscess; immunocompromised patient: Treat locally as above. Incise abscesses. Treat with antibiotics: cloxacillin PO Children: 50 mg/kg/day in 3 divided doses for 7 days Adults: 3 g/day in 3 divided doses for 7 days
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For patients allergic to penicillin: erythromycin PO Children: 30 to 50 mg/kg/day in 3 divided doses for 7 days Adults: 3 g/day in 3 divided doses for 7 days
Quarantine from school. Treat any pre-existing skin disease: lice (see page 101), scabies (see page 98), eczema (see page 117), herpes (see page 116), scalp ringworm (see page 104), or an ENT infection (see Chapter 2). Trace and treat contacts. Check for proteinuria (use a reagent strip) 3 weeks after the infection.
A necrotising perifollicular infection, usually due to Staphylococcus aureus. Development is favoured by humidity, breaks in the skin, lack of hygiene, diabetes mellitus, malnutrition, iron deficiency or compromised immunity.
Clinical features
Furuncle: red, warm, painful nodule with a central pustule, usually around a hair follicle. It becomes fluctuant, discharges a core of purulent exudate, and leaves a depressed scar. It occurs most frequently on the thighs, groin, buttocks, armpits, neck and back. There is no fever. Carbuncle: a cluster of interconnected furuncles, sometimes with fever and peripheral adenopathies. It leaves a depressed scar.
Treatment
For a single furuncle: Clean with soap and water 2 times/day and cover with a dry dressing. Warm moist compresses encourage furuncle to drain. After drainage, clean and apply an antiseptic until the lesion has completely healed.
For furuncles on the face, carbuncles, multiple furuncles (furunculosis) or in immunocompromised patients, treat systematically with antibiotics: cloxacillin PO Children: 50 mg/kg/day in 3 divided doses for 7 days Adults: 3 g/day in 3 divided doses for 7 days For patients allergic to penicillin: erythromycin PO Children: 30 to 50 mg/kg/day in 3 divided doses for 7 days Adults: 3 g/day in 3 divided doses for 7 days For all cases: Frequent hand washing, wash bedding; Never manipulate a furuncle on the face as there is a risk of serious complication: unilateral facial inflammation with high fever and risk of cavernous sinus thrombosis.
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4. Skin diseases
Erysipela
Erysipela is an acute non-necrotising hypodermal infection, due to group A streptococcus. Common in adults, rare in children.
Clinical features
Painful, inflammatory, oedematous plaque on a lower limb, high fever, peripheral adenopathies and lymphangitis). May occur on the face: bilateral, oedematous plaques, with peripheral swelling. Look for a cutaneous portal of entry: ulcer, wound, intertrigo. Local complications: most commonly superficial abscess, sometimes deep abscess (secondary staphylococcal infection), rarely develops into necrotising faciitis. Rare generalised complications: septicaemia, acute glomerulonephritis, erythema nodosum.
Treatment
Hospitalise patients who show marked generalised signs, signs of local complications, patients in poor general condition (chronic disease, the elderly) or if there is a risk of non-compliance during outpatient treatment. For all patients: Bed rest with the affected leg elevated. Non-steroidal anti-inflammatory drugs (NSAID) are contra-indicated (risk of necrotising fasciitis). Treat the portal of entry (ulcer, wound, intertrigo). Check for proteinuria, on reagent strip, 3 weeks after the infection. Note: other bacteria (Staphylococcus aureus, Gram negative bacteria) may cause acute cellulitis resembling erysipela. In the event of treatment failure with penicillin, consider these infections and change to amoxicillin/clavulanic acid (co-amoxiclav).
benzylpenicillin procaine IM Children: 50 000 IU/kg once daily Adults: 1.5 MIU once daily until the fever disappears and there is clinical improvement, then change to oral treatment to complete 7 to 10 days of treatment with: phenoxymethylpenicillin (penicillin V) PO Children under 1 year: 250 mg/day in 4 divided doses Children from 1 to 5 years: 500 mg/day in 4 divided doses Children from 6 to 12 years: 1 g/day in 4 divided doses Adults: 2 g/day in 4 divided doses or amoxicillin PO: 50 mg/kg/day in 2 or 3 divided doses For patients allergic to penicillin: erythromycin PO Children: 50 mg/kg/day in 2 or 3 divided doses for 7 to 10 days Adults: 3 g/day in 3 divided doses for 7 to 10 days
107
Clinical features
Intensely painful, poorly demarcated, erythematous plaque with oedema and severe septic syndrome. Some patients then develop hemorrhagic blisters and bluish or blackish, cold, hypoaesthetic spots. The presence of gas or crepitation on palpation is linked to certain bacteria (Clostridium perfringens, enterobacteria).
Treatment
Urgent surgical drainage of the wound and excision of the necrotic tissue.
Antibiotic treatment (the length of treatment varies according to the clinical evolution): Necrotising fasciitis: benzylpenicillin IV Children: 600 000 IU (360 mg)/kg/day in 6 injections or infusions given every 4 hours Adults: 24 MIU (14.4 g)/day in 6 injections or infusions given every 4 hours + clindamycin IV Children: 40 mg/kg/day in 3 infusions given every 8 hours (maximum 1.3 g/day) Adults: 1.8 g/day in 3 infusions given every 8 hours Gas gangrene: benzylpenicillin IV: as above + metronidazole IV Children: 30 mg/kg/day in 3 infusions given every 8 hours (maximum 1.5 g/day) Adults: 1.5 g/day in 3 infusions given every 8 hours + gentamicin IM Children and adults: 3 to 6 mg/kg/day in 2 injections
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4. Skin diseases
Cutaneous anthrax
A toxic infection of herbivores due to Bacillus anthracis that is transmitted to humans by inoculation through the skin (contact with infected dead animals, flies). Cutaneous anthrax is common in the tropics.
Pulmonary (transmitted by inhalation) and intestinal (transmitted by eating infected meat) forms also exist.
Clinical features
Papule, then pruritic vesicle that ulcerates and becomes a black eschar surrounded by significant oedema with lymphangitis, regional adenopathy and/or generalised signs. Cutaneous anthrax usually occurs on uncovered areas of the body (head, neck, limbs) and is painless. If not treated promptly, there is a risk of extensive, malignant oedema and septicaemia.
Treatment
phenoxymethylpenicillin (penicillin V) PO Children under 1 year: 250 mg/day in 4 divided doses for 7 to 10 days Children from 1 to 5 years: 500 mg/day in 4 divided doses for 7 to 10 days Children from 6 to 12 years: 1 g/day in 4 divided doses for 7 to 10 days Adults: 2 g/day in 4 divided doses for 7 to 10 days
Cutaneous anthrax with extensive oedema or generalised signs or cutaneous anthrax localised on the head or neck (at hospital level):
benzylpenicillin procaine + benzylpenicillin or benzylpenicillin procaine IM
For patients allergic to penicillin: doxycycline PO (except for children under 8 years and pregnant or lactating women) Children over 8 years and adults: 200 mg/day in 2 divided doses for 7 to 10 days or erythromycin PO Children: 30 to 50 mg/kg/day in 2 or 3 divided doses for 7 to 10 days Adults: 2 to 3 g/day in 2 or 3 divided doses for 7 to 10 days
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Cutaneous anthrax
For patients allergic to penicillin: chloramphenicol IV Children: 100 mg/kg/day in 3 injections Adults: 3 g/day in 3 injections Change to oral treatment as soon as possible with chloramphenicol PO at the same doses to complete 10 days of treatment.
Change to oral treatment as soon as possible with phenoxymethylpenicillin (penicillin V) PO to complete 10 days of treatment: Children under 1 year: 250 mg/day in 4 divided doses Children from 1 to 5 years: 500 mg/day in 4 divided doses Children from 6 to 12 years: 1 g/day in 4 divided doses Adults: 2 g/day in 4 divided doses
Prevention
Antibiotic prophylaxis for adult contacts: doxycycline PO (except for pregnant and lactating women): 200 mg/day for 6 weeks
110
4. Skin diseases
Treponematoses
Bacterial infections caused by 3 different types of treponema (other than Treponema pallidum). Human-to-human transmission may be direct or indirect. For treatment of syphilis see Genital infections, page 229.
The 3 non-venereal treponematoses result in positive syphilis serology (TPHAVDRL), but this test is not necessary as diagnosis is clinical.
Clinical features
Treatment
For patients allergic to penicillin: erythromycin PO Children: 50 mg/kg/day in 2 or 3 divided doses for 14 days Adults: 2 to 3 g/day in 2 or 3 divided doses for 14 days or doxycycline PO (except for children under 8 years and pregnant and lactating women) Children over 8 years: 100 to 200 mg once daily or in 2 divided doses for 14 days Adults: 200 mg once daily or in 2 divided doses for 14 days
benzathine benzylpenicillin IM Children under 6 years: 600 000 IU as a single injection Children over 6 years and adults: 1.2 MIU as a single injection
Notes: Antibiotic treatment will cure early stage cases and may relieve the pain of osteitis. It may be ineffective for late stage infections. Syphilis serology will remain positive despite clinical cure. Examine contacts and treat with benzathine benzylpenicillin IM as a single dose as above (also treat patients in the latent stage with positive serology in endemic zones).
111
112
Treponematoses
YAWS
Pathogen
Treponema pertenue
Geographic distribution
Arid areas, semi-desert of the Middle East and Africa Nomadic populations, particularly children
Population Annular, erythematous, scaly plaques, usually on uncovered body parts (face, extremities), resemble dermatophytes. Lesions heal spontaneously leaving scars.
First stage
Yaws chancre: skin coloured lesion, non-indurated, itchy, on the lower limbs in 95% of cases, with peripheral adenopathy. Spontaneous healing or development of a large yaw surrounded by smaller yaws.
Discrete chancre: moist papule, most commonly on the mucous membranes or in dermal folds, with peripheral adenopathy.
Second stage
Lesions appear 3 weeks after the initial chancre, occur in crops and heal spontaneously: frambesioma (papillomatous lesion, vegetal, very contagious) isolated or associated with yaws (round, squamous papules, not very contagious) osteoperiostitis of the long bones (phalanges, nasal process of the maxilla, tibia) Symmetrical white patches on the limbs. The depigmentation is permanent, remaining after treatment.
Pintids: plaques of various colours (bluish, mucous patches of the mouth common: reddish, whitish). May occur anywhere on the very contagious ulcerated, round in body. form, indurated, with white coating, bleed easily, usually occur on the inside of the lips, cheek and tongue or labial folds condyloma in the anogenital region (rare) cutaneous lesions are rare: vegetal aspect, in dermal folds bone destruction identical to that of yaws, in the legs and forearms After several years of latency: gummatous lesions of skin and long bones plantar and palmar keratosis juxta-articular nodules hyper- and hypo-pigmented patches (as in pinta)
Late stage
After some years of latency: periostitis; painful, debilitating osteitis; ulcerating and disfiguring rhinopharyngitis; juxta-articular nodules
4. Skin diseases
Clinical features
Leprosy should be considered in any patient presenting with hypopigmented skin lesions or peripheral neuropathy. In suspect cases, conduct a thorough clinical examination: skin and mucous membranes (patient must be undressed) neurological examination: sensitivity to light touch, pinprick and temperature (hotcold test) palpation of the peripheral nerves Different clinical forms and classification of leprosy exist. The Ridley-Jopling classification differentiates 5 forms based on several factors, including the bacteriological index. The WHO clinical classification is simplified to include only 3 forms (see next page) The Ridley-Jopling classification of leprosy
Borderline B.B. Paucibacillary forms (least contagious forms) B.T. Multibacillary forms (most contagious forms) B.L.
Tuberculoid T.T.
Borderline Tuberculoid
Borderline Lepromatous
Lepromatous L.L.
Tuberculoid leprosy
The primary characteristic is peripheral nerve involvement: tender, infiltrated and thickened nerves; loss of thermal, then tactile and pain sensation. This may lead to trophic ulcers and mutilations of the extremities. Lesions are single or few in number: plaque with a well-demarcated raised border and an atrophic, clear centre or erythematous macule on pale skin, hypopigmented macule on dark skin Nerve involvement develops late in the disease. Lepromatous leprosy The primary characteristic is multiple muco-cutaneous lesions: macules, papules or infiltrated nodules on the face, ear lobes and the upper and lower limbs. Lesions are bilateral, symmetrical, pigmented. Initially, there is no sensory loss. involvement of the nasal mucosa with crusting and nose bleeds oedema of the lower limbs Nerve involvement develops late in the disease.
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Leprosy
Borderline leprosy
Forms between tuberculoid and lepromatous. Indeterminate leprosy (I) Form that does not fall in the Ridley-Jopling classification, frequent in children: a single well-demarcated macule, hypopigmented on dark skin, slightly erythematous on pale skin. Absence of sweat and hair, and loss of sensation are inconstant. Lesion heals spontaneously or the disease evolves towards tuberculoid or lepromatous leprosy. Lepra reactions Reversal reactions: occur in patients with borderline leprosy, during treatment, when evolving towards tuberculoid leprosy. Skin lesions become swollen and painful with a risk of necrosis and ulceration. Acute painful neuritis (ulnar nerve) requires urgent treatment (see page 115) as there is a risk of permanent sequelae. Downgrading reactions: occur in untreated patients with borderline leprosy, when the disease evolves towards lepromatous leprosy. These reactions are difficult to distinguish from reversal reactions. Erythema nodosum leprosum: crops of tender subcutaneous nodules, purplish-red, then yellowish in colour. This reaction is seen exclusively in patients with lepromatous leprosy during the first year of treatment.
In order to simplify diagnosis and to promote rapid implementation of treatment, the WHO simplified clinical classification of leprosy and differentiates only 3 forms: Multibacillary leprosy: more than 5 skin lesions Paucibacillary leprosy: 2 to 5 skin lesions Single skin lesion paucibacillary leprosy
Laboratory
Demonstration of acid-fast bacilli in a Ziehl-Neelsen stained smear: nasal smear skin-split smear taken from the ear lobe or from a skin lesion In tuberculoid leprosy, bacilli are usually not found.
4. Skin diseases
Treatment recommended by the WHO, based on the simplified clinical classification of leprosy
Multibacillary leprosy (more than 5 skin lesions) Paucibacillary leprosy (2 to 5 skin lesions) Paucibacillary leprosy (single skin lesion)
Children between dapsone PO: 50 mg once 10 and 14 years daily, self-administered + rifampicin PO: 450 mg once monthly, under supervision + clofazimine PO: 150 mg once monthly, under supervision and 50 mg on alternate days, self-administered Adults
daily, self-administered + rifampicin PO: 300 mg once monthly, under supervision + clofazimine PO: 100 mg once monthly, under supervision and 50 mg 2 times weekly, self-administered
Duration
dapsone PO: 100 mg once daily, self-administered + rifampicine PO: 600 mg once monthly, under supervision + clofazimine PO: 300 mg once monthly, under supervision and 50 mg once daily, self-administered
12 months
6 months
single dose
Reversal or downgrading reactions: prednisolone (or prednisone) PO: 1 mg/kg/day for 3 to 5 days then progressively decrease the dosage (reduce the dosage by 10% each week).
Erythema nodosum leprosum: clofazimine PO, 100 to 300 mg/day associated with an NSAID (do not administer dosages equal to or greater than 300 mg/day for more than 3 months).
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Clinical features
Recurrent herpes labialis: tingling feeling followed by an eruption of vesicles on an erythematous base, located on the lips (fever blisters) and around the mouth, they may extend onto the face. Recurrence corresponds to a reactivation of the latent virus after a primary infection. No associated malaise, adenopathy or fever. Carefully consider other sites: buccal (page 92), genital (page 236), ophthalmic, and secondary bacterial infections.
Treatment
Clean with soap and water 2 times/day until the lesions have healed. For patients with secondary bacterial infections: antibiotic treatment as for impetigo (see page 105).
Clinical features
Unilateral neuralgic pain followed by an eruption of vesicles on a erythematous base, that follow the distribution of a nerve pathway. Lesions most commonly occur on the thorax, but herpes zoster may also develop on the face with a risk of ophthalmic complications. Herpes zoster is more common in adults than in children. Similar to that of herpes simplex, with the addition of systematic analgesics: paracetamol PO (see Pain, page 29). aciclovir PO given within the first 48 hours after the eruption of lesions is only indicated for severe forms: necrotic or extensive lesions or lesion on the face which may spread to the eyes (see HIV infection and AIDS, page 219).
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Treatment
4. Skin diseases
Treatment
Then apply: for acute eczema: calamine lotion 2 times/day for chronic eczema: zinc oxide ointment 2 times/day
Look for and treat any pre-existing skin disease (scabies, lice etc.).
For patients with secondary infections: treat as impetigo (see page 105).
For patients with intense pruritus, antihistamines (promethazine PO or chlorphenamine PO at the dosages indicated below) for a few days.
Urticaria
Papules: transient, erythematous, oedematous, pruritic, resembling nettle stings. Look for a cause: food or drug (particularly antibiotic) allergy, insect bites; the invasive stage of a bacterial or parasitic infection (ascariasis, strongylodiasis, ancylostomiasis, schistosomiasis, loiasis), viral infection (hepatitis B or C); generalised disease (cancer, lupus, dysthyroidism, vasculitis). If the pruritus is intense, antihistamines: promethazine PO Children from 2 to 5 years: 10 mg/day in 2 divided doses Children from 5 to 10 years: 10 to 25 mg/day in 2 divided doses Children over 10 years and adults: 75 mg/day in 3 divided doses or chlorphenamine PO Children from 1 to 2 years: 1 mg 2 times daily Children from 2 to 6 years: 1 mg 4 to 6 times daily (max. 6 mg/day) Children from 6 to 12 years: 2 mg 4 to 6 times daily (max. 12 mg/day) Children over 12 years and adults: 4 mg 4 to 6 times daily (max. 24 mg/day) In the event of anaphylactic reaction, see page 19.
Treatment
117
Pellagra
Pellagra is a dermatitis resulting from niacin and/or tryptophane deficiency (in persons whose staple food is sorghum, maize not treated with lime; patients with malabsorption, or during famine).
Clinical features
Dark red plaques, well demarcated, symmetric, located on exposed areas of the body (forehead, neck, forearms, legs). The skin becomes very scaly, pigmented, sometimes with haemorrhagic bullae. Gastrointestinal (glossitis, stomatitis and diarrhoea) and neuropsychiatric symptoms are seen in more serious forms.
Traitement
In the event of an epidemic of pellagra, for example in a refugee camp, it is vital that the food ration be modified (add groundnuts or dry vegetables) in order to meet the daily requirements (approximately 15 mg/day for adults).
nicotinamide PO Children and adults: 300 to 500 mg/day in 2 divided doses, give with a diet rich in protein until the patient is fully cured.
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CHAPTER 5
Eye diseases
Xerophthalmia (vitamin A deficiency) Conjunctivitis Trachoma Other pathologies Loiasis Pterygium Cataract Onchocerciasis 121 123 126 128
5. Eye diseases
Clinical features
The first sign is hemeralopia (crepuscular blindness): the child cannot see in dim light, may bump into objects and/or show decreased mobility.
Then, other signs appear gradually: Conjunctival xerosis: bulbar conjunctiva appears dry, dull, thick, wrinkled and insensitive Bitots spots: greyish foamy patches on the bulbar conjunctiva, usually in both eyes (specific sign, however not always present). Corneal xerosis: cornea appears dry and dull Corneal ulcerations Keratomalacia (the last and most severe sign of xerophthalmia): softening of the cornea, followed by perforation of the eyeball and blindness (extreme care must be taken during ophthalmic examination due to risk of rupturing cornea).
Treatment
It is essential to recognise and treat early symptoms to avoid the development of severe complications. Vision can be saved provided that ulcerations affect less than a third of the cornea and the pupil is spared. Even if deficiency has already led to keratomalacia and irreversible loss of sight, it is imperative to administer treatment, in order to save the other eye and the life of the patient. Retinol (vitamin A) PO Regardless of the clinical stage: Children from 6 to 12 months (or under 8 kg): 100 000 IU once daily on D1, D2 and D8 Children over 1 year (or over 8 kg): 200 000 IU once daily on D1, D2 and D8 Adults (except pregnant women): 200 000 IU once daily on D1, D2 and D8 Vitamin A deficiency is rare in breast fed infants under 6 months, if needed: 50 000 IU once daily on D1, D2 and D8.
In pregnant women, treatment varies according to the stage of illness: Hemeralopia or Bitot's spots: 10 000 IU once daily or 25 000 IU once weekly for at least 4 weeks. Do not exceed indicated doses (risk of foetal malformations). If the cornea is affected, risk of blindness outweighs teratogenic risk. Administer 200 000 IU once daily on D1, D2 and D8.
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Xerophthalmia
Corneal lesions are a medical emergency. In addition to the immediate administration of retinol, treat or prevent secondary bacterial infections: apply 1% tetracycline eye ointment twice daily (do not apply eye drops containing corticosteroids) and protect the eye with an eye-pad after each application.
Prevention
Systematically administer retinol PO to children suffering from measles (one dose on D1 and D2). In areas where vitamin A deficiency is common, routine supplementation of retinol PO: Children under 6 months: 50 000 IU as a single dose Children from 6 to 12 months: 100 000 IU as a single dose every 4 to 6 months Children from 1 to 5 years: 200 000 IU as a single dose every 4 to 6 months Mothers after giving birth: 200 000 IU as a single dose immediately after delivery or within 8 weeks of delivery
Note : to avoid excessive dosage, record any doses administered on the health/ immunisation card and do not exceed indicated doses. Vitamin A overdose may cause raised intracranial pressure (bulging fontanelle in infants; headache, nausea, vomiting) and, in severe cases, impaired consciousness and convulsions. These adverse effects are transient; they require medical surveillance and symptomatic treatment if needed.
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5. Eye diseases
Conjunctivitis
Conjunctivitis is an acute inflammation of the conjunctiva due to a bacterial or viral infection, allergy, or irritation. Endemic or epidemic, conjunctivitis may be associated with measles or rhinopharyngitis in children. In the absence of hygiene and effective treatment, secondary bacterial infections may develop, affecting the cornea (keratitis) and leading to blindness.
Clinical features
Clinical signs of all conjuctivites include: redness of the eye and irritation. Visual acuity is not affected. Depending on the cause: abundant and purulent secretions, eyelids stuck together on waking, unilateral infection at onset: bacterial conjunctivitis watery (serous) secretions, no itching: viral conjunctivitis excessive lacrimation, eyelid oedema, intense itching: allergic conjunctivitis
In endemic areas, turn both upper eyelids up to check for signs of trachoma (see Trachoma, page 126).
Always check for foreign bodies (subconjunctival or corneal) and remove after administering 0.4% oxybuprocaine anaesthetic eye drops. Never give bottle of eye drops to the patient.
Suspect keratitis if patient reports intense pain (more than is usually associated with conjunctivitis) and photophobia. Instill one drop of 0.5% fluorescein to check for possible ulcerations.
Treatment
Viral conjunctivitis Clean eyes 4 to 6 times/day with boiled water or 0.9% sodium chloride. Apply local antibiotics if there is a (risk of) secondary bacterial infection (see above).
Bacterial conjunctivitis Clean eyes 4 to 6 times/day with boiled water or 0.9% sodium chloride. Apply 1% tetracycline eye ointment 2 times/day into both eyes for 7 days. Never use corticosteroid drops or ointment.
123
Conjunctivitis
Allergic conjunctivitis Local treatment as for viral conjunctivitis. Antihistamines for one to 3 days (promethazine PO or chlorphenamine PO, see page 117). Note: in the event of a foreign body, check tetanus immunisation status.
Neonatal conjunctivitis
Conjunctivitis due to Neisseria gonorrhoeae and/or Chlamydia trachomatis in children born to infected mothers.
Clinical features
Purulent conjunctivitis within the first 28 days of life. Gonococcal conjunctivitis usually occurs 2 to 7 days after birth. The infection is bilateral in 50% of cases, highly contagious and may rapidly lead to severe corneal lesions and blindness. Chlamydial conjunctivitis usually occurs 5 to 14 days after birth. The infection is often unilateral.
Prevention
Note: In case of maternal herpes simplex virus infection at delivery: clean eyelids with sterile 0.9% sodium chloride then, apply 3% aciclovir eye ointment once into both eyes, then wait 12 hours and apply tetracycline.
Immediately at birth: Clean eyelids with sterile 0.9% sodium chloride. Then, apply 1% tetracycline eye ointment once into both eyes.
Treatment
Treatment is urgent and the child should be referred. When immediate hospitalisation is not possible, clean and apply 1% tetracycline eye ointment into both eyes every hour, until systemic treatment is available. At hospital level If possible isolate the newborn for 24 to 48 hours. Treatment of choice is ceftriaxone IM: 50 mg/kg as a single dose (without exceeding 125 mg) if only the eyes are infected. Failing the above, use spectinomycin IM: 25 mg/kg as a single dose (without exceeding 75 mg).
124
At dispensary level
5. Eye diseases
Clean eyes with an isotonic sterile solution (0.9% sodium chloride or Ringer Lactate) to prevent secretions from adhering, and apply 1% tetracycline eye ointment 4 times/day. If systemic treatment is not immediately available, apply 1% tetracycline eye ointment into both eyes every hour until the treatment is available. Treat mother and partner (see Genital infections, page 229) If treatment with ceftriaxone fails, treat for chlamydia: erythromycin PO: 50 mg/kg/day in 2 or 3 divided doses for 14 days
125
Trachoma
Trachoma
Trachoma is a highly contagious keratoconjunctivitis due to Chlamydia trachomatis. The disease is endemic in the poorest rural areas of Africa, Asia, Central and South America and the Middle East.
Infection is usually first contracted early in childhood by direct or indirect contact (dirty hands, contaminated towels, flies). In the absence of hygiene and effective treatment, the inflammation intensifies with successive infections, causing scars and deformities on the upper tarsal conjunctiva. The resulting ingrowing eyelashes (trichiasis) cause corneal lesions followed by permanent blindness, usually in adulthood. The WHO classifies trachoma into 5 stages. Early diagnosis and treatment of first stages is essential to avoid the development of trichiasis and associated complications.
Clinical features
Stage I: trachomatous inflammation - follicular (TF) Presence of five or more follicles in the upper tarsal conjunctiva. Follicles are whitish, grey or yellow elevations, paler than the surrounding conjunctiva. Stage II: trachomatous inflammation - intense (TI) The upper tarsal conjunctiva is red, rough and thickened. The blood vessels, normally visible, are masked by a diffuse inflammatory infiltration or follicles.
Stage III: trachomatous scarring (TS) Follicles disappear, leaving scars: scars are white lines, bands or patches in the tarsal conjunctiva. Stage IV: trachomatous trichiasis (TT) Due to multiple scars, the margin of the eyelid turns inwards (entropion); the eyelashes rub the cornea and cause ulcerations and chronic inflammation. Stage V: corneal opacity (CO) Cornea gradually loses its transparency, leading to visual impairment and blindness.
126
5. Eye diseases
Treatment
Stages I and II: Clean eyes and face several times per day. Antibiotic therapy: The treatment of choice is azithromycin PO: Children over 6 months or over 6 kg: 20 mg/kg as a single dose Adults: 1 g as a single dose Failing the above, apply 1% tetracycline eye ointment: 2 times/day for 6 weeks In children under 6 months or 6 kg: erythromycin PO (40 mg/kg/day in 2 divided doses for 14 days)
Stage IV: surgical treatment While waiting for surgery, if regular patient follow-up is possible, taping eyelashes to the eyelid is a palliative measure that can help protect the cornea. In certain cases, this may lead to permanent correction of the trichiasis within a few months. The method consists in sticking the ingrowing eyelashes to the external eyelid with thin strip of sticking-plaster, making sure that the eyelid can open and close perfectly. Replace the plaster when it starts to peel off (usually once a week); continue treatment for 3 months. Note : epilation of ingrowing eyelashes is not recommended since it offers only temporary relief and regrowing eyelashes are more abrasive to the cornea. Stage V: no treatment
Prevention
Cleaning of the eyes, face and hands with clean water reduces direct transmission and the development of secondary bacterial infections.
127
Other pathologies
Other pathologies
Onchocerciasis (river blindness)
Clinical features and treatment
Ocular lesions result from the invasion of the eye by microfilariae. They generally develop in adults and progress to blindness in the absence of early treatment. Ocular lesions are always associated with onchocercal skin lesions (see page 157). Pruritus, hemeralopia (crepuscular blindness), decrease in visual acuity, narrowing of the visual field, awareness of microfilariae in the visual field (the patient sees little wiggling worms before his eyes). Lesions of the cornea (punctuate, then sclerosing, keratitis), iris (iridocyclitis) or posterior segment (chorioretinopathy and optic atrophy); microfilariae within the anterior chamber or vitreous humor (slit lamp). For treatment, see Onchocerciasis, page 157. Ivermectin treatment may improve anterior segment lesions (sclerosing keratitis, iridocyclitis) and visual acuity. Severe lesions (chorioretinal lesions, optic atrophy) continue to progress despite treatment.
Loiasis
Migration of an adult worm under the palpebral or bulbar conjunctiva (white, filiform worm, measuring 4 to 7 cm in length, mobile) and ocular pruritus, lacrimation, photophobia or eyelid oedema. For treatment, see Loiais, page 159. The migration of the worm is often of very brief duration. Do not attempt to extract it, or administer anaesthetic drops; simply reassure the patient, the event is harmless. Surgical removal is likewise futile if the worm is dead/calcified.
Pterygium
A whitish, triangular growth of fibrovascular tissue extending slowly from the conjunctiva to the cornea. It occurs most frequently in patients who are exposed to wind, dust, or arid climates and never disappears spontaneously.
Two stages: Benign pterygium develops slowly, does not reach the pupil: no treatment. Progressive vascularized pterygium: red and inflamed growth covers the pupil and may impair vision: Clean eye with sterile water or 0.9% sodium chloride. Surgical removal if facilities are available.
Cataract
Opacity of the lens that causes a progressive loss of visual acuity. Cataract is common in the tropics and can occur at a younger age than in Europe. The presence of cataract in both eyes leads to blindness. Surgery is the only treatment.
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CHAPTER 6
Parasitic diseases
Protozoan infections Human african trypanosomiasis American trypanosomiasis Leishmaniases Malaria 131 139 142 144
Intestinal protozoan infections (parasitic diarrhoea) 147 Helminthic infections Flukes Schistosomiases Cestodes Filariasis Nematode infections 149 150 152 154 157
6. Parasitic diseases
Malaria
Malaria is a parasitic infection due to protozoa of the genus Plasmodium, transmitted to humans by the bite of Anopheles mosquitoes. Transmission by transfusion of parasite infected blood and transplacental transmission are also possible. Most infections are due to four species: P. falciparum, P. vivax, P. ovale and P. malariae. All species may cause uncomplicated malaria; severe malaria (defined by the presence of complications) is almost always due to P. falciparum. Clinical suspicion of malaria should be confirmed whenever possible by a parasitological diagnosis. However, treatment of suspected malaria should not be delayed when confirmatory testing is not available: uncomplicated malaria can progress rapidly to severe malaria, and severe malaria may cause death within a few hours if left untreated.
Clinical features
Malaria should always be considered in a patient living in or coming from an endemic area, who presents with fever (or history of fever in the previous 48 hours). Uncomplicated malaria Fever is frequently associated with chills, sweating, headache, muscular ache, malaise, anorexia or nausea. In children, fever may be associated with abdominal pain, diarrhoea and vomiting. Anaemia is frequent in children and pregnant women. Severe malaria In addition to the above, the patient presents with one or more of the following complications: Impaired consciousness, delirium or coma Seizures, generalised or focal (e.g. abnormal eye movements) Prostration (extreme weakness; in children: inability to sit or drink/suck) Respiratory distress: rapid and laboured breathing or slow, deep breathing Circulatory collapse (shock): cold extremities, weak or absent pulse, slow capillary refill time (> 3 seconds), cyanosis Jaundice (check mucosal surfaces of the mouth, conjunctivae and palms) Haemoglobinuria: dark red urine Abnormal bleeding: skin (petechiae), conjunctivae, nose, gums; blood in stools Acute renal failure: urine output < 12 ml/kg/day in children and < 400 ml/day in adults, despite adequate hydration
Patients presenting with any of the above features or with severe anaemia (see page 37) must be hospitalised immediately.
Laboratory diagnosis
Parasitological diagnosis Microscopy Thin and thick blood films enable parasite detection, species identification, quantification and monitoring of parasitaemia. Note : blood films may be negative due to sequestration of the parasitized erythrocytes in peripheral capillaries in severe malaria, as well as in placental vessels in pregnant women.
131
Malaria
Note: even with positive diagnostic results, rule out other causes of fever.
Rapid diagnostic tests (RDTs)1 Rapid tests detect parasite antigens. They give only a qualitative result (positive or negative) and may remain positive several days or weeks following effective treatment.
Additional examinations Haemoglobin (Hb) level: to be measured routinely in all patients with clinical anaemia, and in all patients with severe malaria. Blood glucose level: to be measured routinely to detect hypoglycaemia (< 3 mmol/l or < 55 mg/dl) in patients with severe malaria and those with malnutrition.
P. vivax and P. ovale can cause relapses due to activation of dormant parasites in the liver. A treatment with primaquine3 can be given to eliminate these parasites, after the initial treatment with CQ. However, this treatment is reserved for patients living in areas where re-infection is unlikely, i.e. non-endemic or low transmission areas.
If vomiting precludes oral therapy, treatment is started using IV or IM artesunate or IM artemether (see page 135) or rectal artesunate (see page 134), depending on availability, until the patient can tolerate a complete 3-day oral treatment with an ACT.
1 Most rapid tests detect the following antigens alone or in combination: HRP2 protein specific to P. falciparum;
an enzyme (Pf pLDH) specific to P. falciparum; an enzyme (pan pLDH) common to all 4 plasmodium species. HRP2 may continue to be detectable for 2 to 3 weeks or more after parasite clearance; pLDH remains detectable for several days (up to 2 weeks) after parasite clearance. 2 In general, P. vivax remains sensitive to CQ but resistance is found in Papua New Guinea, the Solomon Islands, Burma, India, Indonesia and East Timor. In these regions, follow national recommendations. 3 Primaquine for 14 days: 0.25 to 0.5 mg/kg once daily in children > 4 years; 15 mg once daily in adults. Primaquine is contra-indicated in individuals with G6PD deficiency. If G6PD deficiency cannot be tested individually, the decision to prescribe primaquine must take into account the prevalence of deficiency in the population. 4 ACT: a combination of artemisinin or one of its derivatives (e.g. artesunate, artemether) with another antimalarial of a different class. 132
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Presentation
Blister child 3-8 years (15 to 24 kg), 12 tab/blister ==> 2 tab twice daily on D1, D2, D3 Blister child 9-14 years (25 to 34 kg), 18 tab/blister ==> 3 tab twice daily on D1, D2, D3 Blister > 14 years-adults (> 34 kg), 24 tab/blister Coformulated tablets Blister children 2-11 months (4.5 to 8 kg), tab of AS 25 mg/AQ base 67.5 mg, 3 tab/blister ==> 4 tab twice daily on D1, D2, D3 ==> 1 tab once daily on D1, D2, D3 ==> 1 tab once daily on D1, D2, D3
On D1, the first dose is given at 0 hour and the 2nd dose at 8-12 hours. Subsequent doses on D2 and D3 are given twice daily (morning and evening). ==> 1 tab twice daily on D1, D2, D3
Dosage
artesunate-amodiaquine (AS-AQ)
Blister children 1-5 years (9 to 17 kg), tab of AS 50 mg/AQ base 135 mg, 3 tab/blister
Blister children 6-13 years (18 to 35 kg), ==> 1 tab once daily on D1, D2, D3 tab of AS 100 mg/AQ base 270 mg, 3 tab/blister Blister 14 years-adults ( 36 kg), ==> 2 tab once daily on D1, D2, D3 tab of AS 100 mg/AQ base 270 mg, 6 tab/blister Co-blister Coblister children 6 years, containing: 3 tab of AS 50 mg + 3 tab of AQ base 153 mg Coblister children 7-13 years, containing: 6 tab of AS 50 mg + 6 tab of AQ base 153 mg Co-blister Coblister children 6 years, containing: 3 tab of AS 50 mg + 1 tab of SP 500/25 mg Coblister children 7-13 years, containing: 6 tab of AS 50 mg + 2 tab of SP 500/25 mg 5-11 months ==> 1/2 tab AS + 1/2 tab AQ once daily on D1, D2, D3 1-6 years ==> 1 tab AS + 1 tab AQ once daily on D1, D2, D3 ==> 2 tab AS + 2 tab AQ once daily on D1, D2, D3 ==> 4 tab AS + 4 tab AQ once daily on D1, D2, D3 2-11 months ==> 1/2 tab AS once daily on D1, D2, D3 + 1/2 tab SP as a single dose on D1 1-6 years ==> 1 tab AS once daily on D1, D2, D3 + 1 tab SP as a single dose on D1 ==> 2 tab AS once daily on D1, D2, D3 + 2 tab SP as a single dose on D1 ==> 4 tab AS once daily on D1, D2, D3 + 3 tab SP as a single dose on D1 ==> 2 tab AS once daily on D1, D2, D3 + 3 tab SP as a single dose on D1 ==> 1 tab once daily on D1, D2, D3 ==> 2 tab once daily on D1, D2, D3 ==> 1 tab once daily on D1, D2, D3 ==> 2 tab once daily on D1, D2, D3 5-6 kg ==> 1/2 tab once daily on D1, D2, D3 7-12 kg ==> 1 tab once daily on D1, D2, D3 ==> 1 tab once daily on D1, D2, D3 ==> 2 tab once daily on D1, D2, D3 ==> 3 tab once daily on D1, D2, D3 ==> 4 tab once daily on D1, D2, D3
Coblister 14 years/adults, containing: 12 tab of AS 50 mg + 3 tab of SP 500/25 mg or Coblister 14 years/adults, containing: 6 tab of AS 100 mg + 3 tab of SP 500/25 mg Coformulated tablets Blister children 6-11 months (5 to 8 kg), tab of AS 25 mg/MQ 55 mg, 3 tab/blister Blister children 1-6 years (9 to 17 kg), tab of AS 25 mg/MQ 55 mg, 6 tab/blister Blister children 7-12 years (18 to 29 kg), tab of AS 100 mg/MQ 220 mg, 3 tab/blister Blister 13 years-adults ( 30 kg), tab of AS 100 mg/MQ 220 mg, 6 tab/blister Coformulated tablets Blister children 5-12 kg, tab of 20 mg DHA/160 mg PPQ, 3 tab/blister Blister children 13-23 kg, tab of 40 mg DHA/320 mg PPQ, 3 tab/blister Blister children 24-35 kg, tab of 40 mg DHA/320 mg PPQ, 6 tab/blister Blister adolescents-adults 36-74 kg, tab of 40 mg DHA/320 mg PPQ, 9 tab/blister Blister adults 75 kg, tab of 40 mg DHA/320 mg PPQ, 12 tab/blister
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Notes: In infants below the age/weight mentioned in the table above, there is little data on efficacy and safety of ACTs. The combinations AL, AS-AQ and DHA-PPQ can be used. The dose should be calculated so as to correspond to 10-16 mg/kg/dose of lumefantrine; 10 mg/kg/day of amodiaquine; 16-26 mg/kg/day of piperaquine). The combination AS-SP should not be used during the first weeks of life. Clinical condition of young children can deteriorate rapidly; it may be preferable to start parenteral treatment straight away (see page 135). In the event of failure of correctly administered treatment with a first line ACT, use another ACT or quinine PO. quinine PO D1 to D7 Children and adults 50 kg: 30 mg/kg/day in 3 divided doses at 8-hour intervals Adults > 50 kg: 1800 mg/day in 3 divided doses at 8-hour intervals
Reduced susceptibility to quinine has been observed in South-East Asia and Amazon region. In these areas, quinine is given in combination with doxycycline or clindamycin: doxycycline PO D1 to D7 Children > 8 years and adults: 200 mg once daily or, in children < 8 years: clindamycin PO D1 to D7 20 mg/kg/day in 2 divided doses Note: P. falciparum is resistant to chloroquine (CQ) in Africa, South America, South-East Asia and Oceania but appears to remain sensitive to CQ in Haiti and the Dominican Republic. In these regions, CQ remains the first line treatment (see non-falciparum malaria, page 132). Symptomatic treatment Paracetamol PO in the event of high fever, see page 26.
At dispensary level: Before transfer, administer the first dose of artesunate or artemether IM (loading dose, see below) or one dose of rectal artesunate: Weight 3-5 kg 6-10 kg 11-20 kg 21-40 kg 41-60 kg 61-80 kg 50 mg artesunate suppository 1 2 200 mg artesunate suppository 1 2 3 4
At hospital level: The drugs of choice are artemisinin derivatives, administered by parenteral route: artesunate IV or IM or, if injectable artesunate is not available, artemether IM.
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For patients in shock: use artesunate IV or, if not available, quinine IV. The intramuscular route is not appropriate.
artesunate
According to the route of administration used: dissolve the powder (vial of 60 mg artesunate) with 1 ml of 5% sodium bicarbonate then add into the vial: 5 ml of 0.9% NaCl to obtain 6 ml of solution containing 10 mg of artesunate/ml, for IV injection or 2 ml of 0.9% NaCl to obtain 3 ml of solution containing 20 mg of artesunate/ml, for IM injection IV injection Artesunate solution 10 mg/ml Weight Dose < 3 kg 0.8 ml 3-4 kg 1.2 ml 5-7 kg 2 ml 8-11 kg 3 ml 12-16 kg 4 ml 17-23 kg 6 ml 24-30 kg 8 ml 31-40 kg 10 ml 41-50 kg 12 ml 51-60 kg 15 ml 61-70 kg 18 ml > 70 kg 21 ml IM injection Artesunate solution 20 mg/ml Weight Dose < 3 kg 0.4 ml 3-4 kg 0.6 ml 5-7 kg 1 ml 8-11 kg 1.5 ml 12-16 kg 2 ml 17-23 kg 3 ml 24-30 kg 4 ml 31-40 kg 5 ml 41-50 kg 6 ml 51-60 kg 7.5 ml 61-70 kg 9 ml > 70 kg 10.5 ml
slow IV (2-3 minutes) or slow IM into the anterior thigh, if IV route is not possible): 2.4 mg/kg on admission then at 12 hours and 24 hours (H0, H12, H24) then once daily. Administer at least 3 doses, then, if the patient can swallow, change to oral route.
or artemether IM (anterior thigh): 3.2 mg/kg on admission (D1) then 1.6 mg/kg once daily. As soon as the patient can swallow, change to oral route.
Weight < 3 kg 3-4 kg 5-6 kg 7-9 kg 10-14 kg 15-19 kg 20-29 kg 30-39 kg 40-49 kg 50-59 kg Loading dose Maintenance dose (3.2 mg/kg on D1) (1.6 mg/kg/day) 0.5 ml 0.3 ml 0.8 ml 0.4 ml 1.2 ml 0.6 ml 1.6 ml 0.8 ml 2.5 ml 1.2 ml 3.2 ml 1.6 ml 20 mg ampoule artemether (20 mg/ml, 1 ml) Loading dose Maintenance dose (3.2 mg/kg on D1) (1.6 mg/kg/day) 1.2 ml 0.6 ml 1.6 ml 0.8 ml 2 ml 1 ml 2.5 ml 1.2 ml 80 mg ampoule artemether (80 mg/ml, 1 ml)
Use a 1 ml syringe graduated in 0.01 ml when the dose required is less than 1 ml.
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After the initial treatment with parenteral artesunate or artemether, administer a 3-day course of ACT5 (see uncomplicated falciparum malaria, page 132).
quinine IV
(the dose is expressed in quinine salt): Loading dose: 20 mg/kg to be administered over 4 hours, then, keep the vein open with an infusion of 5% glucose over 4 hours; then Maintenance dose: 8 hours after the start of the loading dose, 10 mg/kg every 8 hours (alternate quinine over 4 hours and 5% glucose over 4 hours). For adults, administer each dose of quinine in 250 ml of glucose. For children under 20 kg, administer each dose of quinine in a volume of 10 ml/kg of glucose. Do not administer a loading dose to patients who have received oral quinine, mefloquine or halofantrine within the previous 24 hours: start with maintenance dose. As soon as the patient can tolerate oral treatment, administer either a 3-day course of ACT5 or oral quinine ( doxycycline or clindamycin, see page 134) to complete 7 days of treatment. If the combination AS-MQ is used as oral completion treatment following IV quinine, an interval of 12 hours should elapse between the last dose of quinine and the administration of MQ.
or
Note: in isolated areas, when it is absolutely impossible to transfer a patient to a facility where parenteral antimalarial treatment can be administered, artesunate suppositories must be administered once daily, until the patient is able to take a 3-day course of ACT. Symptomatic treatment and management of complications Hydration Maintain adequate hydration. As a guide, volume to be administered per 24 hours by oral or IV route: Weight Total volume/24 hours Total volume/24 hours if associated severe pneumonia or neurological symptoms 120 ml/kg 80 ml/kg 5 to 9 kg 10 to 19 kg 80 ml/kg 60 ml/kg 20 to 29 kg 60 ml/kg 50 ml/kg 50 ml/kg 40 ml/kg 30 kg
Adjust the volume according to clinical condition in order to avoid dehydration or fluid overload (risk of pulmonary oedema). When the IV route is used, administer 0.9% sodium chloride combined with 10% glucose. Treat dehydration, if present (pages 316 to 321). Fever Paracetamol in the event of high fever, see page 26. Severe anaemia Blood transfusion is indicated: In children with Hb < 4 g/dl (or between 4 and 6 g/dl with signs of decom pensation6). In pregnant women with Hb < 7 g/dl (before 36 weeks) or Hb < 8 g/dl (at 36 weeks or later).
5 Do not use AS-MQ if the patient developed neurological signs during the acute phase. 6 Clinical signs of decompensation may include: shock, impaired consciousness or respiratory distress (acidosis).
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In other patients with Hb < 7 g/dl, monitor clinical status and Hb level and consider transfusion on a case-by-case basis. Hypoglycaemia If the patient is able to swallow: 50 ml of 10% glucose, or 40 ml of water + 10 ml of 50% glucose, or 50 ml of water + 5 g (1 teaspoon) of granulated sugar, or 50 ml of milk. In an unconscious patient: Children: 5 ml/kg of 10% glucose7 by slow IV injection (5 minutes) or infusion Adults: 1 ml/kg of 50% glucose by slow IV injection (5 minutes) Check blood glucose level after 30 minutes. If blood glucose level remains < 3 mmol/l or < 55 mg/dl, administer another dose or give glucose by oral route, according to the patients clinical condition. Hypoglycaemia may recur: maintain regular sugar intake (5% glucose, milk, according to circumstances) and continue to monitor for several hours.
Notes: In an unconscious or prostrated patient, in case of emergency or when venous access is unavailable or awaited, use granulated sugar by the sublingual route to correct hypoglycaemia.8 The risk of hypoglycaemia is higher in patients receiving IV quinine. Coma Check/ensure the airway is clear, measure blood glucose level and assess level of consciousness (Blantyre or Glasgow coma scale). In the event of hypoglycaemia or if blood glucose level cannot be measured, administer glucose. If the patient does not respond to administration of glucose, or if hypoglycaemia is not detected: Exclude meningitis (lumbar puncture) or proceed directly to administration of an antibiotic (see Meningitis, page 165). Insert a urinary catheter; place the patient in the recovery position. Reposition the patient every 2 hours; ensure eyes and mouth are kept clean and moist, etc. Monitor vital signs, blood glucose level, level of consciousness, urine output, hourly until stable, then every 4 hours. Monitor fluid balance. Seizures See page 23. Address possible causes (e.g. hypoglycaemia; fever in children). Respiratory distress Rapid laboured breathing: Check for pulmonary oedema, which may occur with or without fluid overload: reduce IV infusion rate if the patient is receiving IV therapy, nurse semi-sitting, oxygen, furosemide IV: 1 mg/kg in children, 40 mg in adults. Repeat after 1 to 2 hours if necessary. Associated pneumonia should also be considered (see Pneumonia, page 66).
7 In children, if ready-made G10% solution is not available: add 10 ml of G50% solution per 100 ml of G5% 8 Place a level teaspoon of sugar, moistened with a few drops of water, under the tongue, then place the patient in
the recovery position. Repeat after 15 min if the patient has not regained consciousness. As with other methods for treating hypoglycaemia, maintain regular sugar intake, and monitor. 137
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Slow, deep breathing (acidosis): Look for dehydration (and correct if present), decompensated anaemia (and transfuse if present). Oliguria and acute renal failure Look first for dehydration (page 315), especially due to inadequate fluid intake or excessive fluid losses (high fever, vomiting, diarrhoea). Treat dehydration, if present (pages 316 to 321). Be aware of the risk of fluid overload and acute pulmonary oedema. Monitor for the return of urine output.
Acute renal failure (ARF) is found almost exclusively in adults and is more common in Asia than Africa. ARF should be suspected if urine output remains < 400 ml/day or < 20 ml/hour (< 12 ml/kg/day in children) despite adequate rehydration. Insert a urinary catheter, measure output. Restrict fluids to 1 litre/day (30 ml/kg/day in children), plus additional volume equal to urine output. Renal dialysis is often necessary.
Severe malaria During the first trimester, artemisinin derivatives or quinine may be used. During the 2 nd and 3 rd trimesters, the treatment of choice is an arteminisine derivative; quinine is an alternative.
Uncomplicated falciparum malaria During the first trimester, quinine PO for 7 days ( clindamycin) is in principle preferred as it is better known. However, ACT may be used if necessary (except DHA/PPQ), e.g. if quinine is not available, or if the treatment failed or if adherence to quinine treatment is uncertain. During the 2 nd and 3 rd trimesters, the treatment of choice is an ACT (except DHA/PPQ); quinine is an alternative.
Prevention
In areas with high risk of infection with P. falciparum, pregnant women should be tested for malaria at regular interval during antenatal clinic visits. All women with a positive test should receive a 3 day-course of ACT. Women with negative(s) test(s) should receive SP (as a single dose) for its preventive effect, according to a specific schedule (refer to the MSF handbook, Obstetrics), but only in regions where SP still has sufficient efficacy. In malaria endemic zones and in epidemic-prone contexts, all in-patient facilities (including HIV treatment centres and feeding centres), should be furnished with long-lasting insecticidal nets (LLINs).
9 See specialised literature for information regarding anti-vector measures and prevention in travellers.
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Clinical features
Inoculation may be followed by an immediate local reaction (trypanosomal chancre). This chancre arises in about 50% of all rhodesiense but rarely in gambiense. Gambiense HAT Incubation lasts from a few days to several years. The first stage (haemolymphatic stage) corresponds to the haematogenous and lymphatic dissemination of the parasite. Signs include intermittent fever, joint pain, lymphadenopathy (firm, mobile, painless lymph nodes, mainly cervical), hepatosplenomegaly and skin signs (facial oedema, pruritus). The second stage (meningoencephalitic stage) corresponds to the invasion of the central nervous system. Signs of the haemolymphatic stage recede or disappear and varying neurological signs progressively develop: sensory disturbances (deep hyperaesthesia), psychiatric disorders (apathy or agitation), disturbance of the sleep cycle (with daytime somnolence alternating with insomnia at night), impaired motor functions (paralysis, seizures, tics) and neuroendocrine disorders (amenorrhoea, impotence). In the absence of treatment: cachexia, lethargy, coma and death. Rhodesiense HAT The first stage is the same as above, but the incubation period is shorter (< 3 weeks), the disease evolves more rapidly and symptoms are more severe. Patients often die of myocarditis in 3 to 6 months without having developed signs of the meningo encephalitic stage.
In practice, gambiense and rhodesiense HAT can be difficult to differentiate: e.g., there exist cases of acute gambiense infection and others of chronic rhodesiense infection.
Laboratory
Diagnosis involves 3 steps for gambiense HAT (screening test, diagnostic confirmation and stage determination) and 2 steps for rhodesiense HAT (diagnostic confirmation and stage determination). The recommended screening test for T.b. gambiense infection is the CATT (Card Agglutination Test for Trypanosomiasis). It detects the presence of specific antibodies in the patients blood or serum.
139
Diagnostic confirmation: presence of trypanosomes in lymph node aspirates or in blood using concentration techniques: capillary tube centrifugation technique (Woo test), quantitative buffy coat (QBC), mini-anion exchange centrifugation technique (mAEC). Stage determination: detection of trypanosomes (after centrifugation) and white cell count in the cerebrospinal fluid (lumbar puncture): Haemolymphatic stage: no trypanosomes AND 5 white cells/mm3 Meningoencephalitic stage: evidence of trypanosomes OR > 5 white cells/mm3
Due to the toxicity of trypanocides, detection of the parasite is essential before initiating treatment. In the absence of parasitological confirmation, treatment may nevertheless be justified in certain cases: very strong clinical suspicion, patients in life-threatening condition, strong serological suspicion (CATT 1:16 positive) in a population where the disease is highly prevalent (> 2%). Several treatment regimens exist. Check national recommendations and local resistance levels. Treatment must be administered under close medical supervision. Patients receiving pentamidine can be treated as outpatients but those receiving suramin, eflornithine (with or without nifurtimox) or melarsoprol should be hospitalised. After treatment, patients should be checked every 6 months (clinical examination, lumbar puncture and examination for trypanosomes) over 24 months, to look for relapse.
suramin slow IV Children and adults: D1: test dose of 4 to 5 mg/kg D3, D10, D17, D24, D31: 20 mg/kg without exceeding 1 g/injection Suramin may cause anaphylactic reactions, a test dose is recommended prior to starting treatment. In the event of an anaphylactic reaction after the test dose, the patients must not be given suramin again.
IM Children and adults: 4 mg/kg once daily for 7 to 10 days Patients should receive a source of glucose (meal, sweet tea) one hour before injection (risk of hypoglycaemia); they should remain supine during administration and one hour after injection (risk of hypotension). Rhodesiense HAT
Before administrating trypanocides, the priority is to improve the patients general condition (rehydration, treatment of malaria, intestinal worms, malnutrition, bacterial infections). It is nonetheless recommended not to postpone the trypanocidal treatment for more than 10 days. Children and adults: 15 mg/kg/day in 3 divided doses for 10 days + eflornithine IV infusion over 2 hours Children and adults: 400 mg/kg/day in 2 divided infusions (every 12 hours) for 7 days
140 nifurtimox PO
Gambiense HAT
6. Parasitic diseases
In the event of a relapse after NECT or eflornithine: melarsoprol slow IV Children and adults: 2.2 mg/kg once daily for 10 days Prednisolone PO (1 mg/kg once daily) is frequently combined throughout the duration of treatment. Melarsoprol is highly toxic: reactive encephalopathy (coma, or recurrent or prolonged seizures) in 5 to 10% of treated patients, fatal in around 50% of cases; peripheral neuropathy, invasive diarrhoea, severe skin rash, phlebitis, etc. Rhodesiense HAT
melarsoprol slow IV Children and adults: 2.2 mg/kg once daily for 10 days Prednisolone PO (1 mg/kg once daily) is frequently combined throughout the duration of treatment.
Second choice: eflornithine IV infusion over 2 hours Children under 12 years: 600 mg/kg/day in 4 divided infusions (every 6 hours) for 14 days Adults: 400 mg/kg/day in 4 divided infusions (every 6 hours) for 14 days
The catheter must be handled with great attention to avoid local or general bacterial infections: thoroughly disinfect the insertion site, ensure secure catheter fixation, protect the insertion site with a sterile dressing, systematically change the catheter every 48 hours or earlier in case of signs of phlebitis.
All trypanocides are potentially toxic for the mother and the foetus (risk of miscarriage, malformation, etc.). However, due to the life-threatening risk for the mother and the risk of mother-to-child transmission, treatment must be initiated as follows: Haemolymphatic stage: pentamidine for gambiense HAT as of the second trimester and suramin for rhodesiense HAT.
Meningoencephalitic stage: Treatment depends on the mother's condition: If in immediately life-threatening condition: treatment with NECT or eflornithine cannot be deferred until after delivery. If not immediately life-threatening condition: pentamidine for gambiense HAT and suramin for rhodesiense HAT. Treatment with NECT or eflornithine is to be administered after delivery.
Individual protection against tsetse fly bites: long sleeves and trousers, repellents, keeping away from risk areas (e.g. near rivers). Disease control: mass screening and treatment of patients ( T.b. gambiense ), trypanocide treatment of cattle (T.b. rhodesiense), vector control using tsetse fly traps or insecticides.
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American trypanosomiasis
disease)
Chagas disease is a zoonosis due to the flagellated protozoan parasite Trypanosoma cruzi, transmitted to man by triatomine bugs (reduviidae) through a break in the skin or mucous membranes. Transmission by contaminated blood transfusion and transplacental transmission are also possible.
The disease is only found on the American continent in the area between the south of Mexico and the south of Argentina.
Clinical features
Acute phase Depending on the inoculation site, the first sign is a skin chancre or unilateral purplish orbital oedema (Romaa's sign) with local lymphadenopathy and fever (38C, higher in children) over several weeks. This is followed by multiple lymphadenopathies, hepatosplenomegaly, myocarditis (chest pain, heart failure), sometimes meningoencephalitis (seizures, paralysis). Acute phase may be asymptomatic or subclinical. The transition from the acute to chronic phase does not always occur.
Chronic phase Follows a long latent period after the acute phase: cardiac lesions (arrhythmia and conduction disorders, cardiomyopathy, heart failure, chest pain, thromboembolism) and gastrointestinal lesions (megaoesophagus and megacolon). Most patients are asymptomatic.
Laboratory
Acute phase Thin or thick film: detection of the parasite in blood or lymph nodes. Serologic tests: detection of anti-Trypanosoma cruzi antibodies.
Chronic phase
Xenodiagnosis: examination of the faeces of uninfected triatomine bug fed with the patient's blood. Serologic tests: detection of anti-Trypanosoma cruzi antibodies.
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Treatment
Acute phase
nifurtimox PO (contra-indicated in the first trimester of pregnancy, breast-feeding or in patients with history of mental disorders or seizures): Patient under 40 kg: 10 to 12 mg/kg/day in 2 to 3 divided doses for 30 to 60 days Patient over 40 kg: 8 mg/kg/day in 2 to 3 divided doses for 30 to 60 days The adverse effects of nifurtimox (anorexia, nausea, gastric pain, agitation, sleeping disorders, seizures) occur in less than 20% of cases and must not result in treatment discontinuation. Avoid alcohol during treatment. or benznidazole PO (contra-indicated in the first trimester of pregnancy and breastfeeding): Patient under 40 kg: 7.5 mg/kg/day in 2 to 3 divided doses for 30 to 60 days Patient over 40 kg: 5 mg/kg/day in 2 to 3 divided doses for 30 to 60 days The minor adverse effects of benznidazole (nausea, skin rash) occur in about 50% of patients. In the event of purpura with fever, paraesthesia or peripheral polyneuritis, stop treament. benznidazole PO
Children under 40 kg: 7.5 mg/kg/day in 2 to 3 divided doses for 30 to 60 days Children over 40 kg: 5 mg/kg/day in 2 to 3 divided doses for 30 to 60 days
Symptomatic treatment
Do not treat in the event of pregnancy, breast-feeding, hepatic or renal failure, or a severe intercurrent pathology. nifurtimox PO: 8 to 10 mg/kg/day in 2 to 3 divided doses for 60 to 90 days or benznidazole PO: 5 mg/kg/day in 2 to 3 divided doses for 60 days See seizures (page 23), pain (page 29) and heart failure (page 294).
Prevention
Improvement of housing and vector control: plastered walls and cement floors, corrugated-iron roofs, insecticide spraying. Blood transfusions: screening donor blood for T. cruzi infection.
143
Leishmaniases
Leishmaniases
The leishmaniases are a group of parasitic diseases caused by protozoa of the genus Leishmania, transmitted by the bite of a sandfly. Over 20 species cause disease in man. Mucocutaneous leishmaniasis occurs in Latin America and, more rarely, in Africa (Ethiopia, Sudan). Cutaneous leishmaniasis is endemic in more than 70 countries in South and Central America, Middle East, Central Asia, and Africa. Visceral leishmaniasis occurs in more than 60 countries in East and North Africa, South and Central Asia, Southern Europe, and South and Central America.
Clinical features
Cutaneous and mucocutaneous leishmaniasis Single or multiple lesions on the uncovered parts of the body: an erythematous papule begins at the sandfly bite, enlarges to a nodule and extends in surface and depth to form a scabbed ulcer. Ulcers are painless, unless there is secondary bacterial or fungal infection. Usually, lesions heal spontaneously, leaving a scar, and result in lifelong protection from disease. Lesions may also spread to the mucosa (mouth, nose, conjunctiva) giving rise to the mucocutaneous form, which may cause severe disfigurement. Visceral leishmaniasis Visceral leishmaniasis (kala azar) is a systemic disease, resulting in pancytopenia, immunosuppression, and death if left untreated. Prolonged (> 2 weeks) irregular fever, splenomegaly, and weight loss are the main signs. Other signs include: anaemia, diarrhoea, epistaxis, lymphadenopathy, moderate hepatomegaly. Bacterial diarrhoea, pneumonia, and tuberculosis may develop due to immunosuppression. Post-kala azar dermal leishmaniasis Macular, nodular or papular skin rash of unknown aetiology, particularly on the face, and typically occurring after apparent cure of visceral leishmaniasis.
Laboratory
Cutaneous and mucocutaneous leishmaniasis Parasitological diagnosis: identification of Giemsa-stained parasites in smears of tissue biopsy from the edge of the ulcer. No useful serological tests.
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Visceral leishmaniasis
Parasitological diagnosis: identification of Giemsa-stained parasites in smears of splenic, bone marrow, or lymph node aspiration-biopsy. Splenic aspiration is the most sensitive technique but carries a theoretical risk of potentially fatal haemorrhage. Serological diagnosis: rK39 dipstick test and direct agglutination test (DAT) can be used for diagnosis of primary visceral leishmaniasis in clinically suspect cases. Diagnosis of relapse is only by parasitological confirmation.
The various species of Leishmania respond differently to drugs. Follow national recommendations. For information: Cutaneous and mucocutaneous leishmaniasis Cutaneous lesions generally heal spontaneously in 3 to 6 months. Treatment is only indicated if lesions are persistent (> 6 months), disfiguring, ulcerating, or disseminated. Forms with a single lesion or few lesions: start with local treatment with a pentavalent antimonial: sodium stibogluconate or meglumine antimoniate, 1 to 2 ml infiltrated into the lesion if it is a nodule and into the edges and base around the crust if it is an ulcer. It should be repeated every 3 to 7 days for 2 to 4 weeks. Once healing begins, the treatment can be stopped and healing will continue. IM treatment with a pentavalant antimonial (20 mg/kg/day for 10 to 20 days) is restricted to severe cases and must be administered under close medical supervision.
Treatment
Miltefosine PO (as for visceral leishmaniasis) for 28 days is effective in many forms of cutaneous leishmaniasis. Mucocutaneous forms: as for visceral leishmaniasis. Visceral leishmaniasis Visceral leishmaniasis in East Africa
Ulcers are often secondarily infected with streptococci and staphylococci: administer suitable antibiotics.
Treatment in HIV co-infected patients: liposomal amphotericin B IV infusion: 3 to 5 mg/kg/day for 6 to 10 days up to a total dose of 30 mg/kg
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Second-line treatment for relapse and for specific vulnerable groups: severe disease, pregnant women, patients over 45 years: liposomal amphotericin B IV infusion: 3 to 5 mg/kg/day for 6 to 10 days up to a total dose of 30 mg/kg
First-line treatment: a pentavalent antimonial IM or slow IV: 20 mg/kg/day for 17 days + paromomycin IM: 15 mg (11 mg base)/kg/day for 17 days
Leishmaniases
Visceral leishmaniasis in South Asia First-line treatment: liposomal amphotericin B IV infusion: 3 to 5 mg/kg/day for 3 to 5 days up to a total dose of 15 mg/kg or liposomal amphotericin B IV infusion: 10 mg/kg as a single dose Second-line treatment for relapse: liposomal amphotericin B IV infusion: 3 to 5 mg/kg/day for 5 to 8 days up to a total dose of 25 mg/kg For all patients with visceral leishmaniasis, hydration, nutritional support and treatment of intercurrent infections (malaria, dysentery, pneumonia, etc.) are essential. Tuberculosis and/or HIV infection may also be present and should be suspected if relapse occurs more than once or in the event of treatment failure. Post-kala azar dermal leishmaniasis (PKDL) Only patients with severe or disfiguring disease or with lesions remaining for > 6 months, and young children with oral lesions that interfere with feeding, are treated. PKDL in East Africa a pentavalent antimonial IM or slow IV: 20 mg/kg/day for 17 to 60 days + paromomycin IM: 15 mg (11 mg base)/kg/day for 17 days or liposomal amphotericin B IV infusion: 2.5 mg/kg/day for 20 days or miltefosine PO for 28 days (as for visceral leishmaniasis) may be beneficial in HIV coinfected patients PKDL in South Asia 30 mg/kg
liposomal amphotericin B
+ miltefosine PO for 28 days: Children 2 to 11 years: 2.5 mg/kg/day Children > 11 years and < 25 kg: 50 mg/day Children and adults 25 to 50 kg: 100 mg/day Adults > 50 kg: 150 mg/day
Prevention
Insecticide-treated mosquito nets. Vector control and elimination of animal reservoir hosts.
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6. Parasitic diseases
Intestinal protozoa are transmitted by the faecal-oral route (soiled hands, ingestion of food or water contaminated with faeces) and may cause both individual cases of diarrhoea and epidemic diarrhoea outbreaks.
Clinical features
Amoebiasis gives rise to bloody diarrhoea, see Chapter 3, page 88. Clinical presentation of giardiasis, cryptosporidiosis, cyclosporiasis and isosporiasis is very similar: Diarrhoea is usually mild and self-limiting, except in children and patients with advanced HIV disease (CD4 < 200). These patients are likely to develop severe, intermittent or chronic diarrhoea that may be complicated by malabsorption with significant wasting (or failure to gain weight in children) or severe dehydration. Stools are usually watery, but steatorrhoea (pale, bulky, fatty stools) may be found in the event of secondary fat malabsorption; stools may contain mucus. Diarrhoea is usually associated with non-specific gastrointestinal symptoms (abdominal distension and cramps, flatulence, nausea, anorexia), but patients have low-grade fever or no fever.
Laboratory
Definitive diagnosis relies on parasite identification in stool specimens (trophozoites and cysts for giardia; oocysts for cryptosporidium, cyclospora, isospora). Two to three samples, collected 2 to 3 days apart are necessary, as pathogens are shed intermittently.
Treatment
Correct dehydration if present (for clinical features and management, see pages 315 and 321).
147
PO as a single dose or metronidazole PO for 3 days Children: 50 mg/kg (max.2 g) Children: 30 mg/kg/day in 3 divided doses Adults: 2 g Adults: 2 g/jour en une prise
Isoporiasis
PO for 7 days Children: 50 mg SMX + 10 mg TMP/kg/day in 2 divided doses Adults: 1600 mg SMX + 320 mg TMP/day in 2 divided doses In immunocompetent patients, symptoms usually resolve spontaneous in 1 to 3 weeks. Treatment is given in case of severe or prolonged symptoms. PO for 7 to 10 days Adults: 1600 to 3200 mg SMX + 320 to 640 mg TMP/ day in 2 divided doses In immunocompetent patients, symptoms usually resolve spontaneous in 2 to 3 weeks. Treatment is given in case of severe prolonged symptoms.
co-trimoxazole
If reliable stool examination cannot be carried out: parasitic diarrhoeas cannot be differentiated on clinical grounds, nor is it possible to distinguish these from nonparasitic diarrhoeas. An empirical treatment (using tinidazole or metronidazole and cotrimoxazole as above, together or in succession) may be tried in the case of prolonged diarrhoea or steatorrhoea. In patients with HIV infection, see empirical treatment, page 213.
In patients with advanced HIV disease, cryptosporidiosis, cyclosporiasis and isosporiasis are opportunistic infections; the most effective intervention is the treatment of the underlying HIV infection with antiretrovirals. Patients remain at high risk for dehydration/death until immunity is restored.
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Flukes
Clinical features/Diagnosis
praziquantel PO
Infection/Epidemiology
Hepatobiliary flukes Fasciola hepatica and gigantica Distribution: worldwide, in areas where sheep and cattle are raised Transmission: eating uncooked aquatic plants
Lung flukes Paragonimus sp Distribution: South-East Asia, China, parts of Cameroon, Nigeria, Gabon, Congo, Colombia, Peru Transmission: eating raw freshwater crustaceans
The two most prominent symptoms are prolonged (> 2 weeks) productive cough and intermittent haemoptysis (rusty-brown sputum). In endemic areas, paragonimosis should be considered whenever pulmonary tuberculosis is suspected as the clinical and radiological features overlap. Paragonimosis is confirmed when eggs are detected in sputum (or possibly in stools).
triclabendazole PO
Treatment
Children > 2 years and adults: 75 mg/kg/day in 3 divided doses for 2 to 3 days
Opisthorchis felineus (Asia, Eastern Europe) Opisthorchis viverrini (Cambodia, Laos, Vietnam, Thailand) Clonorchis sinensis (China, Koera, Vietnam) Transmission: eating raw/undercooked freshwater fish
During migration phase: asthenia, prolonged fever, myalgia, right upper quadrant pain, mid hepatomegaly; sometimes, allergic signs (e.g. pruritus). At this stage, the diagnosis is rarely considered and can only be confirmed through serology; parasitological examination of stools is always negative. Once adult flukes are present in the biliary tract: presentation resembles cholelithiasis: right upper quadrant pain, recurrent episodes of obstructive jaundice/febrile cholangitis. The diagnosis is confirmed when parasite eggs are detected in stools (or flukes are seen in the biliary tract with sonography).
Children and adults: 10 mg/kg as a single dose May repeat in 24 hours in the event of severe infection
praziquantel PO
Abdominal pain and diarrhoea. With heavy infection, hepatobiliary symptoms: hepatomegaly, right upper quadrant pain, jaundice or episodes of febrile cholangitis. The diagnosis is confirmed when parasite eggs are detected in stools.
Children > 2 years and adults: 75 mg/kg/day in 3 divided doses for 1 or 2 days
praziquantel PO
Intestinal flukes Fasciolopsis buski (India, Bangladesh, South-East Asia) Heterophyes heterophyes (South-East Asia, Nile delta) Metagonimus yokogawai (Siberia, China, Korea) Transmission: eating uncooked aquatic plants (F. buski), raw/undercooked fish (other species)
Symptoms are limited to diarrhoea and epigastric or abdominal pain. With massive infection, F. buski can cause oedematous allergic reactions (including ascites, anasarca). The diagnosis is confirmed when parasite eggs are detected in stools.
Children > 2 years and adults: 75 mg/kg/day in 3 divided doses for 1 day
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149
Schistosomiases
Schistosomiases
Schistosomiases are acute or chronic visceral parasitic diseases due to 5 species of trematodes (schistosomes). The three main species infecting humans are Schistosoma haematobium, Schistosoma mansoni and Schistosoma japonicum. Schistosoma mekongi and Schistosoma intercalatum have a more limited distribution (see table next page).
Humans are infected while wading/bathing in fresh water infested with schistosome larvae. Symptoms occurring during the phases of parasite invasion (transient localized itching as larvae penetrate the skin) and migration (allergic manifestations and gastrointestinal symptoms during migration of schistosomules) are frequently overlooked. In general, schistosomiasis is suspected when symptoms of established infection become evident (see table next page). Each species gives rise to a specific clinical form: genito-urinary schistosomiasis due to S. haematobium, intestinal schistosomiasis due S. mansoni, S. japonicum, S. mekongi and S. intercalatum. The severity of the disease depends on the parasite load. Heavily infected patients are prone to visceral lesions with potentially irreversible sequelae. Children aged 5 to 15 years are particularly at risk: prevalence and parasite load are highest in this age group. An antiparasitic treatment should be administered to reduce the risk of severe lesions, even if there is a likelihood of re-infection. Geographic distribution of schistosomiasis in Africa (WHO)
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Parasite/Epidemiology
The same antiparasitic treatment is used for all species:
Treatment
Genito-urinary schistosomiasis
Intestinal schistosomiasis
S. mansoni Distribution: tropical Africa, Madagascar, the Arabian peninsula, South America (especially Brazil) S. japonicum Distribution: China, Indonesia, the Philippines S. mekongi Distribution: parts of Lao PDR, Cambodia (along the Mekong River) S. intercalatum Distribution: parts of DRC, Congo, Gabon, Cameroon, Chad
Non-specific digestive symptoms (abdominal pain; diarrhoea, intermittent or chronic, with or without blood) and hepatomegaly. For S. intercalatum: digestive symptoms only (rectal pain, tenesmus, rectal prolapse, bloody diarrhoea). If left untreated: risk of hepatic fibrosis, portal hypertension, cirrhosis, gastrointestinal haemorrhage (hematemesis, melanea, etc.), except with S. intercalatum (less pathogenic than other intestinal schistosomes, no severe hepatic lesions). The diagnosis is confirmed when parasite eggs are detected in stools. In the absence of reliable parasitological diagnosis: in areas where intestinal schistosomiasis is common, diarrhoea (especially bloody diarrhoea) with abdominal pain and/or hepatomegaly may be a basis for presumptive diagnosis and treatment.
Urinary manifestations: In endemic areas, urinary schistosomiasis should be suspected in any patients who complain of macroscopic haematuria (red coloured urine throughout, or at the end of, micturition). Haematuria is frequently associated with polyuria/dysuria (frequent and painful micturition). In patients, especially children and adolescents, with urinary symptoms, visual inspection of the urine (and dipstick test for microscopic haematuria if the urine appears grossly normal) is indispensible. Presumptive treatment is recommended in the presence of macro- or microscopic haematuria, when parasitological confirmation (parasite eggs detected in urine) cannot be obtained. Genital manifestations: In women, symptoms of genital infection (white-yellow or bloody vaginal discharge, itching, lower abdominal pain, dyspareunia) or vaginal lesions resembling genital warts or ulcerative lesions on the cervix; in men, haematospermia (blood in the semen). If left untreated: risk of recurrent urinary tract infections, fibrosis/calcification of the bladder and ureters, bladder cancer; increased susceptibility to sexually transmitted infections and risk of infertility. In endemic areas, genito-urinary schistosomiasis may be a differential diagnosis to the genito-urinary tuberculosis, and in women, to the sexually transmitted infections (especially in women with an history of haematuria).
6. Parasitic diseases
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152
praziquantel PO1
Cestodes
Parasites
Diphyllobothriasis Often asymptomatic Diphyllobothrium latum (temperate or cold lake In the event of heavy infection: areas) mild gastrointestinal disturbances, anaemia due to vitamin B12 deficiency associated with (rare) neurological sequelae
Children over 4 years and adults: 5 to 10 mg/kg as a single dose Sometimes gastrointestinal disturbances or (epigastric or abdominal pain, nausea, niclosamide PO diarrhoea) Children: 50 mg/kg as a single dose Adults: 2 g as a single dose Laboratory: eggs in stools or collected from Thoroughly chew the tablets before swallowing perianal skin (scotch tape method), segments and wash down with as little water as possible. in stools
praziquantel PO1
Often asymptomatic
Transmission by eating raw or undercooked Children over 4 years and adults: freshwater fish 10 to 25 mg/kg as a single dose or Individual prevention: cook fish niclosamide PO thoroughly Children: 50 mg/kg as a single dose Adults: 2 g as a single dose Thoroughly chew the tablets before swallowing and wash down with as little water as possible. If anaemia: vitamin B 12 + folic acid Transmission by faecal-oral route or auto-infection
Praziquantel must be administered to pregnant women with T. solium taeniasis and cysticercosis. For the other indications, treatment can usually be deferred until after delivery.
Children over 4 years and adults: In the event of heavy infection: 15 to 25 mg/kg as a single dose gastrointestinal disturbances (epigastric pain) or niclosamide PO Laboratory: eggs in stools Adults: 2 g as a single dose on D1, then 1 g/day for 6 days Thoroughly chew the tablets before swallowing and wash down with as little water as possible.
Prevention: individual: hand washing, nail cutting collective: hygiene and sanitation (water, latrines, etc.)
Cestodes (larvae)
albendazole PO2
Parasites
Individual prevention: treat T. solium carriers hygiene cook meat thoroughly
Treatment
- Muscular: asymptomatic or myalgia - Subcutaneous: nodules - Neurological (neurocysticercosis) headache, convulsions, coma, etc. - Ocular: exophthalmia, strabismus, iritis, etc. Children over 2 years: 15 mg/kg/day in 2 divided doses (without exceeding 800 mg/day) for 8 to 30 days Adults: 800 mg/day in 2 divided doses for 8 to 30 days, repeat if necessary or praziquantel PO3 Children over 4 years and adults: 50 mg/kg/day in 3 divided doses for 14 to 30 days In the event of neurocysticercosis: hospitalize, treat convulsions and combine with prednisolone PO for the entire duration of treatment, starting 2 or 3 days before.
Transmission / Prevention
Hydatid cyst Echinococcus granulosus (South America, North, East and South Africa, Western Europe)
Cysts located in the liver (60% of cases); lungs First-line treatment: surgical excision (30% of cases), and, less frequently, in other sites including the brain. albendazole PO2 is useful in addition to, or instead of, surgery: Long asymptomatic period. The cyst becomes Children over 2 years and adults under symptomatic when complications develop 60 kg: 15 mg/kg/day in 2 divided doses (biliary obstruction; anaphylactic shock in Adults over 60 kg: 800 mg/day in 2 divided the event of rupture into peritoneal cavity, doses vessels or an organ; febrile painful jaundice in the event of rupture into the biliary tree, Treatment duration: etc.) . In addition to surgery (pre-operatively or post-operatively): continuous course of minimum 2 months or at least two 28-day courses with a drug-free interval of 14 days. Inoperable cases: 28-day courses with drugfree intervals of 14 days, for 3 to 6 months (on average), possibly up to 1 year.
Transmission: direct: contact with dogs indirect: water and food contaminated by dog faeces Prevention: individual: avoid contact with dogs collective: eliminate stray dogs, monitor slaughterhouses
6. Parasitic diseases
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154
Nematode infections
Clinical features/Diagnosis
albendazole PO as a single dose
Nematode infections
Ascariasis (roundworms)1 Ascaris lumbricoides Distribution: worldwide, mainly in tropical and subtropical Transmission: ingestion of ascaris eggs
Infection/Epidemiology
Treatment
During larval migration Loefflers syndrome: transient pulmonary symptoms (dry cough, dyspnoea, wheezing) and mild fever. Once adult worms are present in the intestine Abdominal pain and distension. In general, the diagnosis is made when adult worms are expelled from the anus (or occasionally from the mouth). Ascaris are large (15-30 cm), cylindrical worms, pinkish-white, with slightly tapered ends. Complications Ascariasis is usually benign, but massive infestation may cause intestinal obstruction (abdominal pain, vomiting, constipation), especially in children < 5 years. Worms may accidentally migrate to gall bladder, liver or peritoneum, causing jaundice, liver abscess, or peritonitis. Ascaris eggs may be detected through parasitological examination of stools.
albendazole PO for 3 days
Children > 6 months and adults: 400 mg (200 mg in children > 6 months but < 10 kg) or mebendazole PO for 3 days Children > 6 months and adults: 200 mg/day in 2 divided doses (100 mg/day in 2 divided doses in children > 6 months but < 10 kg)
In heavy infection: abdominal pain and diarrhoea In massive infection: chronic bloody diarrhea, tenesmus, rectal prolapse due to frequent attempts to defecate, especially in children. Worms may sometimes be seen on the rectal mucosa when prolapsed: these are grayish-white, 3-5 cm in length, in the shape of a whip, with a thickened body and a long, threadlike extremity. Trichuris eggs may be detected through parasitological examination of stools.
Hookworm infection1 During larval penetration/migration Ancylostoma duodenale Cutaneous signs (pruritic papulo-vesicular rash at the site of penetration, usually the Necator americanus feet) and pulmonary symptoms (similar to ascariasis). Distribution: tropical and Once adult worms are present in the intestine subtropical regions Mild abdominal pain. Attachment of the parasite to the mucosa leads to chronic Transmission: larval skin blood loss and anaemia (in endemic areas, antihelminthic treatment is recommended penetration following contact for patients with iron-deficiency anaemia.) (feet, hands) with contaminated Hookworm eggs may be detected through parasitological examination of stools. soil
ascariasis) is much more effective than mebendazole as a single dose. When using mebendazole, a 3-day treatment (as for ascariasis) is recommended. Treatment of anaemia (see page 37).
Children > 6 months and adults: 400 mg once daily (200 mg once daily in children > 6 months but < 10 kg) or mebendazole PO for 3 days, as for ascariasis. A single dose of albendazole or mebendazole is often insufficient.
1 Roundworms, whipworms and hookworms frequently co-infect the same host. This should be taken into account when prescribing antihelminthic treatment.
Infection/Epidemiology
Clinical features/Diagnosis
First line treatment is ivermectine PO2 as a single dose: Children > 15 kg and adults: 200 micrograms/kg, on an empty stomach
Treatment
While less effective, a 3-day treatment with albendazole PO (as for trichuriasis) may be an alternative.
Enterobiasis (pinworms) Anal pruritus, more intense at night, vulvovaginitis in girls (rare). In practice, the Enterobius vermicularis diagnosis is most often made when worms are seen on the perianal skin (or in the Distribution: worldwide stool in heavy infestation). Pinworms are small (1 cm), mobile, white, cylindrical Transmission: faecal-oral route worms with slightly tapered ends. or auto-infection Pinworm eggs may be collected from the anal area (scotch tape method) and detected under the microscope.
Strongyloidiasis Acute strongyloidiasis Strongyloides stercoralis During larval penetration/migration: cutaneous signs (erythema and pruritus at Distribution: humid tropical the site of penetration, which may persist several weeks) and pulmonary symptoms regions (similar to ascariasis). Transmission: larval skin Once larvae are present in the intestine: gastrointestinal symptoms (bloating, penetration and auto-infection abdominal and epigastric pain, vomiting, diarrhoea). Chronic strongyloidiasis Intestinal larvae may re-infect their host (auto-infection) by penetrating through the intestinal wall or by migrating transcutaneously from perianal skin. Chronic infections result in prolonged or recurrent pulmonary and gastrointestinal symptoms. Transcutaneous migration of intestinal larvae gives rise to a typical rash (larva currens), mainly in the anal region and on the trunk: sinuous, raised, linear, migrating lesion, intensely pruritic, moving rapidly (5 to 10 cm/hour) and lasting several hours or days2. Complications Hyperinfection (massive infestation) results in exacerbation of pulmonary and gastrointestinal symptoms, and possible dissemination of larvae to atypical locations, (CNS, heart, etc.). This form occurs mainly in patients receiving immunosuppressive therapy (e.g. corticosteroids). Strongyloides larvae may be detected through parasitological examination of stools.
Hyperinfections are refractory to conventional therapy. Prolonged or intermittent multiple-dose regimens are required.
ascariasis) or mebendazole PO as a single dose: Children > 6 months and adults: 100 mg (50 mg in children > 6 months but < 10 kg)
6. Parasitic diseases
2 The migrating larvae of Ancylostoma braziliense and caninum (hookworms of cats and dogs) also present as a pruritic, inflammatory, creeping eruption in humans (cutaneous larva migrans) but with a slower rate of progression and a longer duration (several weeks or months). Treatment is with albendazole (400 mg as a single dose or once daily for 3 days in children > 6 months and adults; 200 mg in children > 6 months but < 10 kg) or ivermectin
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Nematode infections
Trichinellosis Enteric phase (1 to 2 days after ingestion of infected meat) Trichinella sp Self-limited episode of diarrhoea and abdominal pain lasting several days. Distribution: worldwide, Muscular phase (about 1 week after ingestion) particularly frequent in Asia High fever; muscular pain (ocular [pain on eye movement], masseters [limitation of (Thailand, Laos, China, etc.) mouth opening], throat and neck [pain with swallowing and speech], trunk and Transmission: consumption of limbs); facial or bilateral peri-orbital oedema; conjunctival haemorrhage, subungual raw or undercooked meat haemorrhage; headache. Typical features are not always present and the patient may containing trichinella larvae present with a non-specific flu-like syndrome. (pork, wart-hog, bear, dog, etc.) Other features, such as dietary habits (consuming pork/raw meat), suggestive symptoms (fever > 39C and myalgia and facial oedema) in several individuals who have shared the same meal (e.g. ceremony) or hypereosinophilia > 1000/mm3, reinforce the clinical suspicion. Definitive diagnosis: muscle biopsy; serology (ELISA, Western Blot).
Infection/Epidemiology
Clinical features/Diagnosis
albendazole PO for 10 to 15 days Children > 2 years: 10 mg/kg/day in 2 divided doses Adults: 800 mg/day in 2 divided doses or mebendazole PO for 10 to 15 days Children > 2 years: 5 mg/kg/day in 2 divided doses Adults: 400 mg/day in 2 divided doses
Treatment
plus, regardless of which antihelminthic is chosen: prednisolone PO: 0.5 to 1 mg/kg/day for the duration of treatment
6. Parasitic diseases
Filariasis
Filariases are helminthiases due to tissue-dwelling nematode worms (filariae). Human to human transmission takes place through the bite of an insect vector. The most important pathogens are outlined in the table below. Mixed infections are common in co-endemic regions. Each filarial species is found in 2 principal developmental stages: macrofilariae (adult worms) and microfilariae (larval offspring). The treatment depends on the pathogenic stage of the species considered and targets microfilariae for O. volvulus and macrofilariae for the other species.
Species /Infections Onchocerca volvulus (onchocerciasis) Wuchereria bancrofti, Brugia malayi and Brugia timori (lymphatic filariasis) Loa loa (loiasis) Subcutaneous nodules Subcutaneous tissue Lymph vessels Location of macrofilariae Location of microfilariae Skin and eye Blood Blood Microfilariae Pathogenic stage Presence of Wolbachia Yes No
Macrofilariae Macrofilariae
Yes
Classical antifilarial agents include diethylcarbamazine (DEC), ivermectin and albendazole. Doxycycline is used solely in the treatment of O. volvulus and lymphatic filarial worms, which harbour an endosymbiotic bacterium ( Wolbachia) sensitive to doxycycline.
Clinical features
In endemic areas, the following signs, alone or in combination, are suggestive of onchocerciasis: Onchocercomas: painless subcutaneous nodules containing adult worms, usually found over a bony prominence (iliac crest, trochanters, sacrum, rib cage, skull, etc.), measuring several mm or cm in size, firm, smooth, round or oval, mobile or adherent to underlying tissue; single, or multiple and clustered. Acute papular onchodermatitis: papular rash, sometimes diffuse but often confined to the buttocks or lower extremities, intensely itchy, associated with scratch marks,
157
Filariasis
often superinfected ( filarial scabies ) 1. This arises from dermal invasion by microfilariae. Late chronic skin lesions: patchy depigmentation on the shins ( leopard skin ), skin atrophy or areas of dry, thickened, peeling skin (lichenification; lizard skin). Visual disturbances and ocular lesions: see page 128.
Laboratory
Detection of the microfilariae in the skin (skin snip biopsy, iliac crest). If the skin biopsy is positive, look for loiasis in regions where loiasis is co-endemic (mainly in Central Africa).
Treatment
Antiparasitic treatment Diethylcarbamazine is contra-indicated (risk of severe ocular lesions). Doxycycline PO (200 mg/day for 4 weeks; if possible 6 weeks) kills a significant percentage of adult worms and progressively reduces the number of O. volvulus microfilariae2. It is contra-indicated in children < 8 years and pregnant or breastfeeding women.
In case of co-infection with Loa loa or in regions where loiasis is co-endemic, ivermectin should be administered with caution (risk of severe adverse reactions in patients with high L. loa microfilarial load): If it is possible to test for Loa loa (thick blood film): Confirm and quantify the microfilaraemia. Administer the appropriate treatment according to the microfilarial load (see Loiasis, page 159). If it is not possible to perform a thick film examination, take a history from the patient: If the patient has received a previous treatment with ivermectin without developing serious adverse reactions (see page 160), administer the treatment. If the patient has never received ivermectin nor developed signs of loiasis (migration of an adult worm under the conjunctiva, or Calabar swellings), administer the treatment. If the patient already has developed signs of loiaisis and if onchocerciasis has a significant clinical impact, administer ivermectin under close supervision (see Loiasis, page 159) or use an alternative (doxycycline, as above). In the case of concomitant lymphatic filariasis: administer ivermectin first then start treatment for lymphatic filariasis with doxycycline PO (see page 162) one week later.
Ivermectin PO is the drug of choice: 150 micrograms/kg as a single dose; a 2nd dose should be administered after 3 months if clinical signs persist. Repeat the treatment every 6 or 12 months to maintain the parasite load below the threshold at which clinical signs appear3. Ivermectin is not recommended in children < 5 years or < 15 kg and pregnant women.
1 Differential diagnosis is sarcoptic scabies (page 98). 2 Elimination of Wolbachia reduces the longevity and fertility of the macrofilariae, and thus the production of new
3 Ivermectin kills microfilariae and disrupts production of microfilariae by adult worms. However the treatment
must be administered at regular intervals since it does not kill adult worms.
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6. Parasitic diseases
Nodules are benign, often deep, and their ablation does not treat onchocerciasis. Thus, nodulectomy is reserved for cranial nodules (their proximity to the eye is a risk factor for visual compromise) or nodules which are cosmetically unacceptable. In other cases, refrain from nodulectomy. Nodulectomy is performed under local anaesthesia, in an appropriately equipped facility.
Loiasis
The distribution of loiasis is linked to that of its vector (Chrysops) in forests or savannah with gallery forests in West or Central Africa (limits West: Benin; East: Uganda; North: Sudan and South: Angola). The subconjunctival migration of an adult worm is pathognomonic of Loa loa infection. Localised subcutaneous swellings, allergic in origin, transient (several hours or days), painless, non-pitting, appearing anywhere on the body, frequently the upper extremities and face, often associated with localised or generalised pruritus ( Calabar swellings ). Onset of pruritus, in the absence of other signs. Subcutaneous migration of an adult worm: pruritic, palpable red cord-like linear lesion, sinuous, advancing (1 cm/hour), disappearing rapidly with no trace4. Such migration generally arises following treatment with diethylcarbamazine, rarely spontaneously.
Clinical features
Laboratory
Detection of microfilariae in the peripheral blood (thick film, stained with Giemsa). Blood specimens should be collected between 10 am and 5 pm. Quantify microfilaraemia even if the diagnosis is certain, since treatment is determined by the intensity of the parasite load. If the thick film is positive, look for onchocerciasis in regions where onchocerciasis is co-endemic (mainly in Central Africa).
Treatment
Antiparasitic treatment Diethylcarbamazine (DEC) is the only macrofilaricide available but is contraindicated in: Patients with microfilaraemia > 2000 mf/ml (risk of severe encephalopathy, with poor prognosis). Patients co-infected with O. volvulus (risk of severe eye lesions). Pregnant women, infants, and patients in poor general condition.
4 For differential diagnosis, see cutaneous larva migrans, page 155.
159
Filariasis
Ivermectin (and possibly albendazole) is used to reduce microfilaraemia before administration of DEC; however, ivermectin administration may trigger encephalopathy in patients with very high Loa loa microfilaraemia (> 30 000 mf/ml). Doxycycline is not indicated since Loa loa does not harbour Wolbachia. Management:
2) L. loa microfilaraemia is between 2,000 and 8,000 mf/ml: Reduce microfilaraemia with ivermectin (150 micrograms/kg as a single dose); repeat the treatment every month if necessary; administer DEC when the microfilaraemia is < 2000 mf/ml. 3) L. loa microfilaraemia is between 8,000 and 30,000 mf/ml: Treatment with ivermectin (150 micrograms/kg as a single dose) may cause marked functional impairment for several days. Close supervision and support from family member(s) are necessary5. Prescribe paracetamol as well for 7 days.
1) L. loa microfilaraemia is < 1,000-2,000 mf/ml: A 28-day treatment of DEC may be started using small doses of 3 to 6 mg/day, i.e. 1/32 or 1/16 of a 100 mg tablet, administered in 2 divided doses. Double the dose every day up to 400 mg/day in 2 divided doses in adults (3 mg/kg/day in children). If microfilaraemia or symptoms persist, a second treatment is given 4 weeks later. If DEC is contra-indicated due to possible or confirmed co-infection with O. volvulus, ivermectin (150 micrograms/kg as a single dose) treats onchocerciasis, and reduces pruritus and frequency of Calabar swellings. The treatment may be repeated every month or every 3 months.
4) L. loa microfilaraemia is > 30,000 mf/ml: If the loiasis is well tolerated, it is preferable to refrain from treatment: the disease is benign and treatment with ivermectin may cause very severe adverse reactions (encephalopathy), albeit rarely. If loiasis has a significant clinical impact and/or the patient presents with symptomatic onchocerciasis requiring treatment, ivermectin (150 micrograms/kg as a single dose) is administered for 5 days under supervision in hospital6. An attempt to first reduce L. loa microfilaraemia using albendazole (400 mg/day in 2 divided doses for 3 weeks) is an option. When L. loa microfilaraemia is < 30 000 mf/ml, treat with ivermectin under close supervision and support, then DEC when the microfilaraemia is < 2000 mf/ml.
Extraction of macrofilariae
Subcutaneous migration of a microfilaria usually results from treatment with DEC; the worm will die beneath the skin and extracting it serves no purpose. Removal of an adult worm from the conjunctiva: see page 128.
5 Patients may present with various pain syndromes, be unable to move without help or unable to move at all.
Monitoring is necessary to determine whether the patient can manage activities of daily living, and provide assistance if necessary. If the patient remains bedridden for several days, ensure pressure sores do not develop (mobilisation, repositioning). 6 A severe reaction may occur on D2-D3. It is usually preceded by haemorrhages of the palpebral conjunctiva on D1-D2. Routinely check for this sign by turning back the eyelids. Symptoms of post-ivermectin encephalopathy are reversible and the prognosis favourable, if the patient is correctly managed; the treatment is symptomatic until symptoms resolve. Avoid the use of steroids due to adverse effects. 160
6. Parasitic diseases
Clinical features
Acute recurrent inflammatory manifestations Adenolymphangitis: lymph node(s) and red, warm, tender oedema along the length of a lymphatic channel, with or without systemic signs (e.g. fever, nausea, vomiting). The inflammation may involve the lower limbs, external genitalia and breast. In men: acute inflammation of the spermatic cord (funiculitis), epididymis and testicle (epididymo-orchitis). Attacks resolve spontaneously within a week and recur regularly in patients with chronic disease. Chronic manifestations Lymphoedema: oedema of the lower extremity or external genitalia or breast, secondary to obstruction of the lymphatics by macrofilariae. The oedema is reversible initially but then becomes chronic and increasingly severe: hypertrophy of the area affected, progressive thickening of the skin (fibrous thickening with formation of creases, initially superficial, but then deep, and verrucous lesions). The final stage of lymphoedema is elephantiasis. In men: increase in volume of fluid due to accumulation within the tunica vaginalis (hydrocoele, lymphocoele, chylocoele); chronic epididymo-orchitis. Chyluria: milky or rice-water urine (disruption of a lymphatic vessel in the urinary tract). In patients parasitized by Brugia spp, genital lesions and chyluria are rare: lymphoedema is usually confined to below the knee. Detection of microfilariae in the peripheral blood (thick film)7; blood specimens should be collected between 9 pm and 3 am. In regions where loiasis and/or onchocerciasis are co-endemic, check for co-infection if the LF diagnosis is positive.
Laboratory
Treatment
Antiparasitic treatment Treatment is not administered during an acute attack.
ultrasound of the inguinal area in search of the filarial dance sign .
7 When test results are negative in a clinically suspect case, consider detection of antigens (ICT rapid test) and/or
161
Filariasis
Diethylcarbamazine PO as a single dose (400 mg in adults; 3 mg/kg in children) may be an alternative but eliminates a variable proportion of adult worms (up to 40%) and does not relieve symptoms; a prolonged treatment is no more effective than single dose therapy. In addition, DEC is contra-indicated in patients with onchocerciasis or Loa loa microfilarial load > 2000 mf/ml and in pregnant and breast-feeding women. Ivermectin (weak or absent macrofilaricidal effect) and albendazole should not be used for the treatment of individual cases (no effect on symptoms). In the case of confirmed or probable co-infection with O. volvulus: treat onchocerciasis first (see page 157), then administer doxycycline. Control/prevention of inflammatory manifestations and infectious complications Acute attacks: bed rest, elevation of the affected limb without bandaging, cooling of the affected limb (wet cloth, cold bath) and analgesics; antibacterial or antifungal cream if necessary; antipyretics if fever (paracetamol) and hydration.
Doxycycline PO, when administered as a prolonged treatment, eliminates the majority of macrofilariae and reduces lymphoedema: 200 mg/day for 4 weeks minimum. It is contra-indicated in children < 8 years and pregnant or breast-feeding women.
Established lymphoedema: bandaging of the affected limb by day, elevation of the affected extremity (after removal of the bandage) when at rest, simple exercises (flexion-extension of the feet when recumbent or upright, rotation of the ankles); skin hygiene, as above. Surgery May be indicated in the treatment of chronic manifestations: advanced lymphoedema (diversion-reconstruction), hydrocoele and its complications, chyluria.
Prevention of episodes of lymphangitis and lymphoedema: hygiene of the affected extremity8, comfortable footwear, immediate attention to secondary bacterial/fungal infections and wounds.
8 Wash at least once daily (soap and water at room temperature), paying special attention to folds and interdigital
areas; rinse thoroughly and dry with a clean cloth; nail care.
162
CHAPTER 7
Bacterial diseases
Bacterial meningitis Tetanus Typhoid fever Brucellosis Plague 165 170 174 176 178 180 182 185
Leptospirosis
7. Bacterial diseases
Bacterial meningitis
Meningitis is an acute bacterial infection of the meninges, which may affect the brain and lead to irreversible neurological damage and auditory impairment. Bacterial meningitis is a medical emergency. The treatment is based on early parenteral administration of antibiotics that penetrates well into the cerebrospinal fluid. Empiric antibiotic therapy is administered if the pathogen cannot be identified or while waiting for laboratory results. The main bacteria responsible vary depending on age and/or context: Meningitis in a non-epidemic context: Children 0 to 3 months: Children 7 days: Gram-negative bacilli ( Klebsiella spp, E. coli, S. marscesens , Pseudomona spp, Salmonella spp) and group B streptococcus Children > 7 days: S. pneumoniae accounts for 50% of all bacterial meningitis. L. monocytogenes is occasionally responsible for meningitis during this period. Children 3 months-5 years: S. pneumoniae, H. influenza B and N. meningitidis Children > 5 years and adults: S. pneumoniae and N. meningitidis
Meningitis in an epidemic context:1 In the Sahelian region 1 during the dry season, epidemics of meningococcal meningitis (Neisseria meningitidis A or C or W135) affect children from 6 months of age, adolescents and adults. In these regions, whether during epidemics or not, all the above pathogens can be found, especially in young children.
Special conditions: Immunodepressed patients (HIV, malnourished): high percentage of Gramnegative bacilli (specially Salmonella spp) and also M. tuberculosis. Sickle cell anaemia: Salmonella spp and Staphylococcus aureus are frequent causes. Meningitis may be related to S. aureus when associated with skin infection or skull fracture.
Clinical features
The clinical presentation depends on the patient's age: Children over 1 year and adults Fever, severe headache, photophobia, neck stiffness Brudzinski's sign (neck flexion in a supine patient results in involuntary flexion of the knees) and Kernig's sign (attempts to extend the knee from the flexed-thigh position are met with strong passive resistance). Petechial or ecchymotic purpura (usually in meningococcal infections) In severe forms: coma, seizures, focal signs, purpura fulminans
1 But not exclusively, e.g. Rwanda, Angola, Brazil
165
Bacterial meningitis
The classic signs of meningitis are usually absent. The child is irritable, appears sick with fever or hypothermia, poor feeding or vomiting. Other features include: seizures, apnoea, altered consciousness, bulging fontanelle (when not crying); occasionally, neck stiffness and purpuric rash.
Laboratory
Macroscopic examination of the cerebrospinal fluid (CSF): antibiotic therapy should be initiated immediately if the LP yields a turbid CSF. Microscopic examination: Gram stain (but a negative examination does not exclude the diagnosis) and white blood cell count (WBC). In an epidemic context, once the meningococcal aetiology has been confirmed, there is no need for routine LP for new cases.
Pressure Aspect Clear
(leucocytes/mm3)
WBC <5
Cloudy, turbid
Normal to + +++
100-20 000 Pandy + mainly neutrophiles 100-500 mg/dl In neonates: > 20 In immunocompromised the WBC may be < 100 10-700 mainly lymphocytes < 500 mainly lymphocytes < 800 mainly lymphocytes Pandy Pandy + Pandy
Protein
Other tests
Gram stain +
++++
Rapid test for detection of bacterial antigens. Note : in an endemic area, it is essential to test for severe malaria (rapid test or thin/thick films).
166
7. Bacterial diseases
2) If the pathogen is unknown: Children < 3 months: 2 weeks beyond the first sterile CSF culture or 21 days Children > 3 months and adults: 10 days. Consider extending treatment or alternative diagnoses if fever persists beyond 10 days. On the other hand, a 7-day course of ceftriaxone is sufficient in patients who are making an uncomplicated recovery.
Additional treatment
Ensure that the patient is well fed and well hydrated (infusions or nasogastric tube if necessary). Seizures: see page 23. Coma: prevention of bed sores, care of the mouth and eyes, etc.
Dexamethasone reduces the risk of hearing loss in patients with H. influenzae or S. pneumoniae . Early administration in indicated in meningitis caused by these pathogens or when the pathogen is unknown, except in neonates (and in presumed meningococcal meningitis in an epidemic context). dexamethasone IV: Children > 1 month and adults: 0.15 mg/kg (max. 10 mg) every 6 hours for 2 days. The treatment should be started before or with the first dose of antibiotic, otherwise, the treatment offers no benefit.
In this context, N. meningitidis is the most likely pathogen. First-line treatment (in outpatients) is either oily chloramphenicol or ceftriaxone administered as a single IM dose.
167
Bacterial meningitis
oily chloramphenicol IM: 100 mg/kg as a single dose without exceeding 3 g. Divide the dose into two injections if needed, half-dose in each buttock. Do not exceed indicated doses.
Children over 2 years and adults (except for pregnant or breast-feeding women)
or
ceftriaxone
IM: 100 mg/kg as a single dose, maximum 4 g. Divide the dose into two injections if needed, half-dose in each buttock. Dose Age 2-5 years 1.5 g 6-9 years 2.5 g 10-14 years 3g 15 years 4g
Dose
Age
6-9 years 2g
15 years 3g
If there is no clinical improvement (i.e. repeated convulsions, fever > 38.5C, appearance or aggravation of a reduced level of consciousness or of neurological signs) 24 hours after the first injection: administer a second dose of the same antibiotic. If there is no clinical improvement (same signs as above) 48 hours after beginning the treatment (i.e. after two consecutive doses of oily chloramphenicol or ceftriaxone administered at 24-hour interval), review the diagnosis. If no other diagnosis has been found (e.g. malaria), continue the treatment with ceftriaxone once daily for 5 days. Children less than 2 years The treatment depends on the most probable pathogen and the patients age, as for meningitis in non-epidemic context (see page 169).
ceftriaxone IM: 100 mg/kg as a single dose, maximum or ampicilline IV at the doses indicated page 169
4g
Additional treatment
Ensure that the patient is well fed and well hydrated (infusions or nasogastric tube if necessary). Seizures: see page XX. Coma: prevention of bed sores, care of the mouth and eyes, etc. Dexamethasone in not indicated.
168
No associated skin infection Alternative IV 75 mg/kg/day in 2 injections + cefotaxime IV 100-150 mg/kg/day in 2 injections
cloxacillin
Associated skin infection (including umbilical cord infection) First choice Alternative
0-7 days
IV 150 mg/kg/day in 3 injections + cefotaxime IV 100-150 mg/kg/day in 2 injections IV 200 mg/kg/day in 3 injections + gentamicin IV 7.5 mg/kg/day in 3 injections IV 200 mg/kg/day in 4 injections + ceftriaxone IV 100 mg/kg once daily
cloxacillin cloxacillin ampicillin
ampicillin
8-28 days
1 month
IV 200 mg/kg/day in 3 injections + cefotaxime IV 150-200 mg/kg/day in 3 injections IV 200-300 mg/kg/day in 3 injections + gentamicin IV 7.5 mg/kg once daily
ampicillin
ampicillin
1 to 3 months
ampicillin
cloxacillin
3 months to 5 years
ceftriaxone
ceftriaxone
IV 200 mg/kg/day in 4 injections 8 to 12 g/day in adults + ceftriaxone IV 100 mg/kg once daily 2 g/day in adults
7. Bacterial diseases
169
Tetanus
Tetanus
Tetanus is a severe infection due to the bacillus Clostridium tetani, which is found in soil, and human and animal waste. The infection is not communicable. C. tetani is introduced into the body through a wound and produces a toxin whose action on the central nervous system is responsible for the symptoms of tetanus. Tetanus is completely preventable through vaccination. In unvaccinated individuals, most breaks in the skin or mucous membranes carry a risk of tetanus, but the wounds with the greatest risk are: umbilical cord stump in newborns, operative sites in surgical or obstetrical procedures performed under non-sterile conditions, puncture wounds, wounds with tissue loss or contamination with foreign material or soil, avulsion and crush injuries, sites of non-sterile injections, chronic wounds (e.g. lower extremity ulcers), burns and bites. Tetanus develops in persons who have not been correctly vaccinated before exposure, or have not received adequate prophylactic treatment immediately after exposure.
Clinical features
Generalised tetanus is the most frequent and severe form of the infection. It presents as muscular rigidity, which progresses rapidly to involve the entire body, and paroxysmal muscle spasms, which are very painful. Level of consciousness is not altered. Children and adults Average period from exposure to onset of symptoms is 7 days (3 to 21 days) Muscular rigidity is first seen in the jaw muscles (difficulty, then inability, in opening the mouth [trismus], preventing the patient from speaking, eating) then, extends to those of the face (fixed smile [risus sardonicus]), the neck (difficulty in swallowing), trunk (restriction of respiratory muscles; hyperextension [opisthotonos]), abdomen (guarding) and limbs (extension of the lower limbs and flexion of the upper limbs). Muscle spasms appear at the onset or when muscular rigidity becomes generalised. They are triggered by stimuli or arise spontaneously. Spasms of the thoracic and laryngeal muscles may cause respiratory distress or aspiration.
Newborns
In 90% of cases, initial symptoms appear within 3 to 14 days of birth. The first signs are significant irritability and sucking difficulties (rigidity of the lips, trismus), then rigidity becomes generalised, as in adults. An infant qualifies as a case of neonatal tetanus if it has sucked and cried normally for the first 2 days of life, then becomes irritable and stops sucking 3 to 28 days after birth, and demonstrates rigidity and muscle spasms. Although the umbilicus is almost always the portal of entry, clinical infection of the cord site (omphalitis) is evident in only one half of cases. Check for septicaemia, which is frequently associated.
170
7. Bacterial diseases
Treatment
Hospitalisation is necessary and requires 3 to 4 weeks on average. Correct management can reduce mortality by 50%, even in hospitals with limited resources. General measures The patient should be the sole occupant of a dark, quiet room: all stimulation (noise, light, touch) may trigger painful spasms that may cause critical respiratory distress. Handle the patient very carefully, under sedation and as little as possible; reposition every 3 to 4 hours to prevent bedsores. Establish IV access: hydration, access for IV injections. Insert a nasogastric tube: hydration and feeding; administration of oral medications. Gentle aspiration of secretions (nose, oropharynx). Provide hydration and nutrition in feeds divided over 24 hours. In newborns, give expressed breast milk every hour (risk of hypoglycaemia). Newborns, children and adults: 500 IU as a single dose, injected into 2 separate sites Inhibition of toxin production The treatment of choice is metronidazole IV for 7 days1 (administered over 60 min in newborns): Newborns: one dose of 15 mg/kg then, after 24 hours, 7.5 mg/kg every 12 hours Children: 7.5 mg/kg every 8 hours Adults: 500 mg every 8 hours Control of rigidity and spasms, and sedation of the patient Due to increased risk of respiratory depression/arrest when using high doses of diazepam, the patient must always be kept under constant close observation, with immediate availability of equipment required for intubation and manual ventilation. The dose and frequency of administration depend on the patients clinical response and tolerance (monitor respiratory rate or oxygen saturation). For IV as well as for intra-rectal administration2, dilute 2 ml of diazepam (10 mg) in 8 ml of 5% glucose or 0.9% sodium chloride. Children: 0.1 to 0.3 mg/kg by slow IV injection (over 3 to 5 minutes) or 0.5 mg/kg by rectal route, without exceeding 10 mg per dose, to be repeated every 1 to 4 hours Adults: 10 mg by slow IV or intra-rectal route
diazepam
1 Benzylpenicillin IV for 10 to 14 days may be an alternative (second choice):
Neutralisation of toxin
Newborns: 80,000 IU/kg/day (50 mg/kg/day) in 2 injections every 12 hours Infants: 125,000 IU/kg/day (75 mg/kg/day) in 3 injections every 8 hours Children: 200,000 to 400,000 IU/kg/day (120 to 240 mg/kg/day) in 4 injections every 6 hours Adults: 10 MIU/day (6 g/day) in 4 injections every 6 hours Change to the oral route when possible with phenoxymethylpenicillin (penicillin V) by nasogastric tube. Children: 62.5 mg/kg/day in 4 doses; adults: 2 g/day in 4 doses. 2 For rectal administration, use a syringe without needle or cut a nasogastric tube, CH8, to a length of 2-3 cm and attach it to the tip of the syringe. 171
Tetanus
In the case of severe spasms not controlled by intermittent dosing, diazepam may be administered by continuous IV infusion (except in infants less than 1 month), under constant close observation. Children over 1 month and adults: 3 to 10 mg/kg/day, the dose is to be adjusted according to clinical response. In early stage, if necessary; the risk of respiratory depression is increased, thus closer monitoring is required: morphine slow IV (5 minutes) Newborns: 0.05 mg/kg every 6 hours if needed Children from 1 to 6 months: 0.1 mg/kg every 6 hours if needed Children over 6 months and adults: 0.1 mg/kg every 4 hours if needed Treatment of the entry site A systematic search should be made for the entry wound. Provide local treatment under sedation: cleansing, and for deep wounds, irrigation, debridement. Cord infection: do not excise or debride; treat bacterial omphalitis. Tetanus vaccination As tetanus does not confer immunity, vaccination against tetanus must be administered once the patient has recovered. In case of neonatal tetanus, initiate the vaccination of the mother. Control of pain
Prevention
1) Post-exposure prophylaxis
In all cases: Cleansing and disinfection of the wound, and elimination of foreign material. Antibiotics are not prescribed routinely for prophylaxis. The decision to administer an antibiotic (metronidazole or penicillin) is made on a case-by-case basis, according to the patients clinical status. Depending on pre-exposure vaccination status: tetanus vaccine (TV)3 and immunoglobulin: see indications below.
Risk Minor clean wound All other wounds Complete vaccination (3 or more doses) Incomplete vaccination (less than 3 doses) Time since administration of latest dose: < 5 years 5-10 years > 10 years or no vaccination or unknown status None None None TV one booster Initiate or complete TV dose
3 Tetanus-containing vaccine, such as TT or DT or dT or DTP or DTP + HepB or DTP + Hib + HepB according to
172
7. Bacterial diseases tetanus vaccine IM Children and adults: 0.5 ml/injection With no vaccination or unknown vaccination status: administer at least 2 doses at an interval of 4 weeks. With incomplete vaccination: administer one dose. Then, to ensure long-lasting protection, administer additional doses to complete the total 5 doses, as indicated in the table below. human anti-tetanus immunoglobulin IM
Children and adults: 250 IU as a single dose; 500 IU for wounds more than 24 hours old. Inject the vaccine and the immunoglobulin in 2 different sites, using a separate syringe for each.
Children: 5 doses in total: a first series of 3 doses of DTP or DTP + HepB or DTP + Hib + HepB before the age of 1 year, administered at an interval of 1 month (e.g. at the age of 6, 10 and 14 weeks), then a 4th dose of a vaccine containing tetanus toxoid between the ages of 4 to 7 years, then a 5th dose between 12 and 15 years. Women of childbearing age: 5 doses during the reproductive years: a series of 3 doses (dT or TT) with an interval of at least one month between the 1st and 2nd dose and an interval of at least 6 months between the 2nd and 3rd dose, then two other doses, each at minimum interval of one year, e.g. during pregnancies (see table below). Pregnant women: if a woman has never been vaccinated or if her vaccination status is unknown: 2 doses of dT or TT during the pregnancy to reduce the risk of tetanus in mother and newborn: the first as soon as possible during the pregnancy and the second at least 4 weeks later and at least 2 weeks before delivery. This vaccination regime protects more than 80% of newborns from neonatal tetanus. A single dose offers no protection. Continue vaccination after delivery to complete 5 doses, as for women of childbearing age.
Dose TV1 TV2 TV3 TV4 TV5 On first contact with the health care system or as soon as possible during pregnancy At least 4 weeks after TV1 6 months to 1 year after TV2 or during the following pregnancy 1 to 5 years after TV3 or during the following pregnancy 1 to 10 years after TV4 or during the following pregnancy Vaccination schedule in adults Degree and duration of protection No protection 80% 1 to 3 years 99% 10 years 95% 5 years
3) Other measures
Typhoid fever
Typhoid fever
Systemic infection due to Salmonella typhi. The organism enters the body via the gastrointestinal tract and gains access to the bloodstream via the lymphatic system. Typhoid fever is acquired by ingestion of contaminated water and food or by direct contact (dirty hands).
Clinical features
Sustained fever (lasting more than one week), headache, asthenia, insomnia, anorexia, epistaxis. Abdominal pain or tenderness, diarrhoea or constipation, gurgles. Toxic confusional state, prostration. Moderate splenomegaly, relative bradycardia (normal pulse despite fever).
Differential diagnosis may be difficult as symptoms resemble those of lower respiratory tract infections, urinary infections, and malaria or dengue fever in endemic areas. Complications can occur during the active phase or during convalescence (even during treatment): intestinal perforation or haemorrhage, peritonitis, myocarditis, encephalitis, coma.
Laboratory
Relative leukopenia (normal white blood cell count despite septicaemia). Isolation of S. typhi from blood cultures (take at least 10 ml of blood) and stool cultures during the first 2 weeks. Widal's agglutination reaction is not used (both sensitivity and specificity are poor).
Keep under close surveillance, hydrate, treat fever (see Fever, page 26).
Antibiotic therapy: case-fatality rates of 10% can be reduced to less than 1% with early antibiotic treatment based on the findings of blood cultures. The oral route is more effective than the parenteral route. If the patient cannot take oral treatment, start by injectable route and change to oral route as soon as possible. Antibiotic treatment (except during pregnancy or breast-feeding) The treatment of choice is: ciprofloxacin PO for 5 to 7 days Children: 30 mg/kg/day in 2 divided doses (usually not recommended in children under 15 years, however, the life-threatening risk of typhoid outweighs the risk of adverse effects) Adults: 1 g/day in 2 divided doses
174
7. Bacterial diseases
cefixime
S. typhi is rapidly developing resistance to quinolones. In this event, use: ceftriaxone IM or IV1 for 10 to 14 days depending on severity Children: 75 mg/kg once daily Adults: 2 to 4 g once daily Antibiotic treatment in pregnant or breast-feeding women In the absence of resistance: amoxicillin PO: 3 g/day in 3 divided doses for 14 days In pregnant women, typhoid carries a major risk of maternal complications (intestinal perforation, peritonitis, septicaemia) and foetal complications (miscarriage, premature delivery, intrauterine death). If resistance: ceftriaxone IM or IV1: 2 to 4 g once daily for 10 to 14 days depending on severity Failing that, use ciprofloxacin PO (usually not recommended for pregnant or breastfeeding women. However, the life-threatening risk of typhoid outweighs the risk of adverse effects). For dosage, see above. Note: fever persists for 4 to 5 days after the start of treatment, even if the antibiotic is effective. It is essential to treat the fever and to check for possible maternal or foetal complications.
Failing that, and in the absence of resistance: for 14 days Children: 75 to 100 mg/kg/day in 3 divided doses Adults: 3 g/day in 3 divided doses or chloramphenicol PO for 10 to 14 days depending on severity Children: 100 mg/kg/day in 3 divided doses Adults: 3 g/day in 3 divided doses
amoxicillin PO
PO for 7 days may be an alternative to ciprofloxacine in children under 15 years: Children over 3 months: 15 to 20 mg/kg/day in 2 divided doses
In patients presenting severe typhoid, with toxic confusional state (hallucinations, altered consciousness) or intestinal haemorrhage: dexamethasone IV: loading dose 3 mg/kg and then 1 mg/kg every 6 hours for 2 days
Prevention
Individual (hand washing) and collective hygiene (safe water supply, sanitation).
The possibility of vaccination must be considered: it can be useful in some situations (high-risk age group, hyperendemic zone), but its effectiveness remains controversial.
1 The solvent of ceftriaxone for IM injection contains lidocaine. Ceftriaxone reconstituted using this solvent must
NEVER
be administered by IV route. For IV administration, water for injection must always be used.
175
Brucellosis
Brucellosis
A zoonosis that mainly affects domestic animals. It is occasionally transmitted to man by ingestion of infected raw milk, or by contact (with infected animals or with soiled objects through abrasion on the skin). Human-to-human transmission is rare. Brucellosis is caused by Gram-negative bacilli of the genus Brucella: B. melitensis (sheep and goats), B. abortus (cattle), B. suis (pigs) and less commonly, B. canis and B. ovis. The disease is found worldwide and mainly in rural areas. The true incidence of brucellosis in tropical countries is probably underestimated as it is often undiagnosed.
Clinical features
The clinical signs and associated symptoms are fluctuating and non specific. Diagnosis is difficult because of the broad spectrum of clinical manifestations. Acute form Common form: gradual onset over one to 2 weeks: undulant fever (up to 39-40C) lasting 10 to 15 days, night sweats, chills, asthenia, joint and muscle pain. Possible sacroileitis, arthritis (knee) and orchitis. In regions where malaria is endemic, the possibility of acute brucellosis should be considered when a high fever persists despite correct anti-malarial treatment. Other clinical forms: Typhoid-like form: sudden onset with signs of septicaemia; high fever, typhoid state, delirium, abdominal signs. Subacute form: mild, non-specific clinical signs that do not lead the patient to seek medical attention. Serum test positive.
Secondary brucellosis Prolonged asthenia, focal signs: Bone and joint involvement: arthritis of the hip, sacroileitis, spondylitis with sciatalgia (pseudo-Pott's disease). Neurobrucellosis: pseudo-tuberculosis meningitis, meningoencephalitis; a complication at vertebral site involving peripheral nerves may cause motor and/or sensory disorders. Chronic brucellosis General signs; physical and mental asthenia, sweating and polyalgia. Focal signs: slow developing bone, neuromeningeal or visceral foci.
Laboratory
During the acute phase diagnosis can be confirmed by the detection of the pathogen in a blood culture. The Rose Bengal test (or card test) can identify specific antibodies. It is a quick, cheap and both specific and sensitive test for the diagnosis of acute and localized forms of brucellosis.
176
7. Bacterial diseases
Other serological tests (Wright's test, ELISA, indirect immunfluorescence and Coombstest) cannot usually be done.
Treatment
Treatment is based on a combination of 2 antibiotics. Since streptomycin and rifampicin are also used in the treatment of tuberculosis, it is essential to rule out the possibility of active TB before starting treatment (patient history, clinical examination and chest X-ray if possible). Rifampicin must only be used when indicated below. Acute form Children over 8 years and adults (except in pregnant or breast-feeding women): doxycycline PO Children: 100 to 200 mg once daily or in 2 divided doses for 6 weeks Adults: 200 mg once daily or in 2 divided doses for 6 weeks + streptomycin IM Children: 15 mg/kg once daily for 2 weeks Adults: 1 g once daily for 2 weeks
Focal brucellosis Same treatment regimen as for the acute form, but for a period of 6 weeks to 3 months depending on severity. Surgical draining of an abscess of the liver or spleen may be indicated. Neurobrucellosis or endocarditis: combination of rifampicin + doxycycline + gentamicin. Antibiotic treatment is not effective in the context of chronic, non-focal brucellosis.
Pregnant or breast-feeding women cotrimoxazole PO: 1600 mg SMX + 320 mg TMP/day in 2 divided doses for 6 weeks + rifampicin PO: 600 mg once daily for 6 weeks Note: In pregnant women, the combination of cotrimoxazole + rifampicin can be administered regardless of the stage of pregnancy if treatment is indispensable. Administration of vitamin K is recommended to prevent neonatal and maternal haemorrhage. phytomenadione (vial containing 10 mg/ml, 1 ml): To the mother: 10 mg/day PO for the 15 days preceding the expected date of delivery To the newborn: 2 mg PO as a single dose at birth and again after 4 to 7 days
Children under 8 years cotrimoxazole PO: 40 mg SMX + 8 mg TMP/kg/day in 2 divided doses for 6 weeks + gentamicin IM: 7.5 mg/kg once daily or in 2 divided doses for 2 weeks or rifampicin PO: 15 mg/kg once daily for 6 weeks
Prevention
Washing of hands and clothing if in contact with animals. Boil milk and avoid eating raw cheese and undercooked meat.
177
Plague
Plague
A zoonosis caused by the Gram-negative bacillus Yersinia pestis that mainly affects wild and domestic rodents. Plague is transmitted to man by the bite of an infected flea vector or through a break in the skin by contact with a rodent. Human-to-human transmission occurs through the bites of human fleas, or, in the case of pneumonic plague, by inhaling infected droplets expelled by coughing. Vast foci of infection remain in Central and Southeast Asia, Africa, Madagascar, and in North and South America.
There are 3 main clinical forms: Bubonic plague is the most common form: high fever, chills, headache, associated with one (or more) very painful lymph node, usually inguinal (bubo). Frequent gastrointestinal signs: abdominal pain, vomiting, diarrhoea, etc. The mortality rate in untreated patients is approximately 50% as a result of septicaemia. Septicaemic plague is a complication of untreated bubonic plague and is a fulminant illness. Pneumonic plague is a very contagious form: high fever, chills, headache, myalgia associated with paroxysmal coughing, haemoptysis and respiratory distress. This form progresses rapidly, and is fatal unless treated. It occurs either as a complication of bubonic plague or as the result of a primary infection. Occasionally, the disease can take the form of meningitic plague.
Laboratory
Isolation of Y. pestis (direct examination and culture) from lymph node aspirate, blood, sputum, cerebrospinal fluid, depending on the form involved. Serodiagnosis: ELISA reads positive soon after the onset of the illness. Transportation of the samples requires a cold chain (failing that, the temperature must be kept below 30C).
When plague is suspected: take samples for cultures and antibiotic sensitivity testing and then treat immediately without waiting for the diagnosis to be confirmed. Inform the health authorities as soon as the diagnosis has been confirmed.
Isolation: Patients suffering from bubonic plague do not have to be isolated. Treat the patient and his/her bedding and clothing with an insecticide (e.g. permethrin 0.5% powder; see Pediculoses, page 101). Observe elementary rules of hygiene (wash hands, wear gowns, gloves etc.). Patients with primary or secondary pneumonic plague must be strictly isolated. Their bedding, clothing, sputum and excreta must be disinfected with a chlorinated solution. Observe elementary rules of hygiene (wash hands, wear hospital lab coats, gloves etc.) and both the patient and carers should wear facemasks.
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7. Bacterial diseases
If treatment is begun early, recovery is rapid and complete. Penicillins, cephalosporins and macrolides should not be used. Aminoglycosides, tetracyclines, chloramphenicol and sulphonamides are effective. Follow national recommendations. For information: streptomycin IM for 10 days Children: 30 mg/kg/day in 2 divided doses given at 12 hour-intervals Adults: 2 g/day in 2 divided doses given at 12 hour-intervals gentamicin IM for 10 days Neonates and children under one year: 7.5 mg/kg/day in 2 divided doses Children over one year: 6 mg/kg/day in 2 divided doses Adults: 3 mg/kg/day in 2 divided doses doxycycline PO for 10 days Children over 8 years and adults: 200 mg/day, once daily or in 2 divided doses chloramphenicol PO or IV for 10 days Children over one year and adults: 50 mg/kg/day in 4 divided doses given at 6 hour-intervals Choice of antibiotics
doxycycline First choice Bubonic plague Indications chloramphenicol or streptomycin chloramphenicol Alternative
streptomycin gentamicin
chloramphenicol
streptomycin
Chemoprophylaxis of contacts
Note: in order to prevent the emergence of resistance to streptomycin which is used in the treatment of tuberculosis, it is preferable to use doxycycline or chloramphenicol for the treatment of bubonic plague. In the event of contact, and within one week after the end of exposure: doxycycline PO throughout the period of contact (minimum 5 days of treatment) Children over 8 years and adults: 100 to 200 mg/day, once daily or in 2 divided doses or co-trimoxazole PO throughout the period of contact (minimum 5 days of treatment) Children: 40 mg SMX + 8 mg TMP/kg/day in 2 divided doses Adults: 1600 mg SMX + 320 mg TMP/day in 2 divided doses
Prevention
Flea vector control is essential to controlling an epidemic. Long-term prevention: environmental sanitation and control of rodent reservoir. Vaccination against plague is only indicated for people with a high risk of exposure (laboratory technicians handling rodents) and can in no circumstances be used as a method for controlling an epidemic.
179
Leptospirosis
Leptospirosis
A zoonosis caused by spirochetes of the genus Leptospira, affecting many domestic and wild animals (particularly rodents and principally rats). Leptospirosis is acquired by indirect contact (contact of the skin or mucous membranes with animal urine-contaminated water, e.g. when swimming) and less commonly, by direct contact with infected animals.
Clinical features
Diagnosis is difficult because of the broad spectrum of clinical manifestations. A distinction is usually made between the mild form (the most common, usually with a favourable outcome) and the severe form (multiple organ dysfunction syndrome).
Mild form After an incubation period of one to 3 weeks: influenza-like illness (high fever, chills, headache, myalgias), often combined with gastrointestinal disorders (anorexia, abdominal pain, nausea, vomiting) and possible pulmonary signs (cough, chest pain). Other signs: conjunctival haemorrhage, hepatosplenomegaly, and multiple adenopathies. Mild jaundice may be present, but this form is usually anicteric. The signs regress after 5 to 6 days, and then reappear, sometimes with meningeal invasion, which may be complicated by encephalitis or myelitis.
Severe form or Weil's syndrome The onset of the disease is the same as in mild form. After a few days, acute hepatorenal manifestations with fever, jaundice, oligo-anuric renal failure; diffuse haemorrhagic syndrome (purpura, ecchymoses, epistaxis etc.), pulmonary signs (cough, chest pain, haemoptysis) and cardiac signs (myocarditis, pericarditis). Temperature chart and progress of leptospirosis ! Temperature!
40 Azotemia! Jaundice! 37! 1! 5! Presence of leptospires!
In the blood! In the CSF! In the urine!
10!
15!
20!
days!
Presence of antibodies!
180
7. Bacterial diseases
Laboratory
Isolation through culture of leptospires from blood, cerebrospinal fluid (during the first phase) or urine (during the second phase). Serodiagnosis: immunofluorescence or ELISA (antibodies are detected from Day 8). Blood cell count: polymorphonuclear leukocytosis. If meningeal syndrome: lumbar puncture yields a clear fluid, usually with raised leucocyte count and elevated protein level (about 1 g/litre). Urine: proteinuria, leukocyturia, possible haematuria and presence of casts.
Treatment
Rest and treatment of fever: paracetamol PO (see Fever, page 26). Acetylsalicylic acid (aspirin) is contraindicated (risk of haemorrhage). Moderate form amoxicillin PO Children: 50 mg/kg/day in 2 or 3 divided doses for 7 days Adults: 2 g/day in 2 or 3 divided doses for 7 days or doxycycline PO (except in pregnant or breast-feeding women and children under 8 years) Children over 8 years: 100 mg/day in 2 divided doses for 7 days Adults: 200 mg/day in 2 divided doses for 7 days or erythromycin PO Children: 50 mg/kg/day in 2 or 3 divided doses for 7 days Adults: 2 to 3 g/day in 2 or 3 divided doses for 7 days
Severe form ampicillin IV Children: 100 mg/kg/day in 3 injections Adults: 4 to 6 g/day in 3 injections Switch to the oral route as soon as possible, with amoxicillin to complete 7 days of treatment. or erythromycin IV Children: 50 mg/kg/day in 3 or 4 injections Adults: 2 g/day in 4 injections Switch to the oral route as soon as possible to complete 7 days of treatment.
Prevention
Avoid bathing in endemic areas. Rodent control, environmental sanitation (particularly water). Vaccination is restricted to personnel exposed in the course of their work.
181
LBRF is caused by Borrelia recurrentis. It occurs in epidemic waves when conditions favourable to the transmission of body lice are met: cold climate/season, overcrowding and very poor sanitation (e.g. refugee camps, prisons). Endemic foci of LBRF are mainly the Sudan and the Horn of Africa (especially Ethiopia). LBRF can be associated with louse-borne typhus (see page 185). The mortality rate for untreated LBRF ranges from 15 to 40%.
Clinical features
Relapsing fever is characterized by febrile episodes separated by afebrile periods of approximately 7 days (4 to 14 days).
The initial febrile episode lasts up to 6 days: Sudden onset of high fever (> 39C), severe headache and asthenia, diffuse pain (muscle, joint, back pain), often associated with gastrointestinal disturbances (anorexia, abdominal pain, vomiting, diarrhoea). Splenomegaly is common; bleeding signs (e.g. petechiae, subconjunctival haemorrhage, epistaxis, bleeding gums), jaundice or neurological symptoms may be observed. The febrile episode terminates in a crisis with an elevation in temperature, pulse and blood pressure, followed by a fall in temperature and blood pressure, which may last for several hours. Following the initial febrile episode, the cycle usually reccurs; each episode is less severe than the previous one and the patient develops temporary immunity. Complications: collapse during defervescence, myocarditis, cerebral haemorrhage; during pregnancy: abortion, preterm delivery, in utero foetal death, neonatal death.
In practice, in an applicable epidemiological setting (see above), a suspect case of LBRF is, according to the WHO, a patient with high fever and two of the following symptoms: severe joint pain, chills, jaundice or signs of bleeding (nose or other bleeding) or a patient with high fever who is responding poorly to antimalarial drugs. Clothing should be checked for the presence of body lice and nits.
182
7. Bacterial diseases
Laboratory
The diagnosis is confirmed by detection of Borrelia in thick or thin blood films (Giemsa stain). Blood samples must be collected during febrile periods. Spirochetes are not found in the peripheral blood during afebrile periods. In addition, the number of circulating spirochetes tends to decrease with each febrile episode.
Treatment
Treatment of pain and fever (paracetamol PO) and prevention or treatment of dehydration in the event of associated diarrhoea. Elimination of body lice is essential in control of epidemics (see page 101).
Antibiotic therapy (suspect or confirmed cases and close contacts): doxycycline PO1 Children: 100 mg as a single dose Adults: 100 or 200 mg as a single dose or erythromycin PO Children 5 years: 250 mg as a single dose Children > 5 years and adults: 500 mg as a single dose
Clinical features
The clinical manifestations and complications of TBRF are similar to those of LBRF but neurological symptoms (particularly, cranial nerve palsies and lymphocytic meningitis) are more frequent than in LBRF and the number of relapses is higher.
The clinical diagnosis is difficult, especially during the first episode: cases occur sporadically rather than in outbreaks; the tick bite is painless and usually unnoticed by the patient; symptoms are very similar to those of malaria, typhoid fever, leptospirosis, certain arbovirosis (yellow fever, dengue) or rickettsiosis, and meningitis.
1 Doxycycline is usually contra-indicated in children under 8 years and pregnant women. However, if
erythromycin is not available, it may be used for the treatment of LBRF, the administration of a single dose should not cause any adverse effects 183
Laboratory
As for LBRF, the diagnosis is confirmed by detection of Borrelia in the patients blood. Repeat the examination if the first smear is negative despite strong clinical suspicion.
Treatment
Treatment of pain and fever (paracetamol PO) and prevention or treatment of dehydration in the event of associated diarrhoea.
Antibiotic therapy: doxycycline PO Children over 8 years: 100 mg/day in 2 divided doses for 5 days Adults (except pregnant women): 200 mg/day in 2 divided doses for 5 days or erythromycin PO Children under 8 years: 50 mg/kg/day in 2 divided doses for 5 days Pregnant women: 2 g/day in 2 divided doses for 5 days
Antibiotic therapy can trigger a Jarisch-Herxheimer reaction with high fever, chills, fall in blood pressure and sometimes shock. It is recommended to monitor the patient for 2 hours after the first dose of antibiotic, for occurrence and management of severe Jarisch-Herxheimer reaction (symptomatic treatment of shock). Jarisch-Herxheimer reaction appears to occur more frequently in LBRF than in TBRF.
184
7. Bacterial diseases
Eruptive rickettsioses
Eruptive fevers caused by bacteria of the genus Rickettsia and transmitted to man by an arthropod vector. Three main groups are distinguished: typhus group, spotted fever group and scrub typhus group.
Detection of specific IgM of each group by indirect immunofluorescence. The diagnosis is confirmed by 2 serological tests at an interval of 10 days. In practice, clinical signs and the epidemiological context are sufficient to suggest the diagnosis and start treatment.
Treatment
Symptomatic treatment: Hydration (PO or IV if the patient is unable to drink) Fever: paracetamol PO (see Fever, page 26). Acetylsalicylic acid (aspirin) is contraindicated due to the risk of haemorrhage. Antibiotherapy1 for 7 days or until 2 days after the fever has disappeared: doxycycline PO (except in children under 8 years and pregnant or breast-feeding women): Children over 8 years: 100 to 200 mg once daily or in 2 divided doses Adults: 200 mg once daily or in 2 divided doses or chloramphenicol PO (except in pregnant or breast-feeding women) Children: 50 to 75 mg/kg/day in 3 divided doses Adults: 2 g/day in 3 divided doses
In pregnant or breast-feeding women: josamycin PO2: 3 g/day in 3 divided doses for 8 days
In a context of epidemic typhus, doxycycline PO 200 mg as a single dose is the choice treatment, but there is a risk of recurrence. Note: doxycycline is usually contraindicated in children under 8 years and in pregnant or breast-feeding women. However, the administration of a single dose should not, in theory, provoke adverse effects. Check national recommendations. Epidemic typhus: control of body lice (page 101). Murine typhus: control of fleas and then rats. Spotted fevers: avoid tick bites by wearing clothing and using repellents. Scrub typhus: use of repellents, chemoprophylaxis with doxycycline PO (200 mg once weekly in adults).
Prevention
1 Unlike borrelioses, antibiotic treatment of rickettsioses does not provoke a Jarisch-Herxheimer reaction.
However, the geographical distribution of borrelioses and rickettsioses may overlap, and thus a reaction may occur due to a possible co-infection (see Borrelioses, page 182). 2 Only some macrolides can be used. Erythromycin is not effective. 185
Clinical features
186
Eruptive rickettsioses
Common to all forms: Sudden onset of fever (temperature of over 39C) with severe headache and myalgias. 3 to 5 days later; onset of generalised cutaneous eruption (see below). Hypotension; non-dissociated rapid pulse (variable). Typhoid state: prostration, omnubilation, confusion and extreme asthenia, particularly marked in typhus forms. Inoculation eschar: painless, black crusted lesion surrounded by a erythematous halo at the site of the bite. Always check for this significant sign. Non-cutaneous signs vary from one form to another, and are atypical and variable (see below).
Spotted fever
Other Old-World tick-borne fevers ticks
Group
Murine typhus R. typhi dogs endemic ticks rodents ticks R. conorii R. rickettsii rat fleas endemic worldwide maculopapular +++ meningeal signs 2 0 black necrotic area +/maculopapular around the mediterranean, Sub-Saharan Africa purpural North America, Central America, Columbia, Brazil rats endemic Mediterranean spotted fever Rocky Mountain spotted fever
Typhus
Scrub typhus
Scrub typhus O. tsutsugamushi rodents mites
Form
Epidemic typhus
Pathogen
R. prowasekii
Vector
Reservoir
body lice
man
Occurence
epidemic
sporadic Southern Africa, Australia, Siberia maculopapular Far-east, India, South Pacific macular
Geographical distribution
Rash
Eschar
maculopapular
+++
+/-
Complications can be severe, and sometimes fatal: encephalitis, myocarditis, hepatitis, acute renal failure, haemorrhage etc.
Extra-cutaneous signs
CHAPTER 8
Viral diseases
Measles Poliomyelitis Rabies Viral hepatitis Dengue fever Viral haemorrhagic fevers HIV infection and AIDS 189 192 194 198 201 204 207
8. Viral diseases
Measles
Measles is a highly contagious acute viral infection, transmitted by the airborne route (inhalation of respiratory droplets spread by infected individuals). The disease mainly affects children under 5 years of age and can be prevented by immunization. For more information, refer to the MSF handbook Management of a measles epidemic.
Clinical features
Prodromal or catarrhal phase (2 to 4 days) High fever (39-40C) with cough, coryza (nasal discharge) and/or conjunctivitis (red and watery eyes). Kopliks spots: tiny bluish-white spots on an erythematous base, found on the inside of the cheek. This sign is specific of measles infection, but may be absent at the time of examination. Observation of Koplik's spots is not required for diagnosing measles.
The eruptive phase is followed by skin desquamation during 1 to 2 weeks, very pronounced on pigmented skin (the skin develops a striped appearance).
Eruptive phase (4 to 6 days) On average 3 days after the onset of symptoms: eruption of erythematous, nonpruritic maculopapules, which blanch with pressure. The rash begins on the forehead then spreads downward to the face, neck, trunk (2nd day), abdomen and lower limbs (3rd and 4th day). As the rash progresses, prodromal symptoms subside. In the absence of complications, the fever disappears once the rash reaches the feet. The rash fades around the 5th day in the same order that it appeared (from the head to the feet).
In practice, a patient presenting with fever and erythematous maculopapular rash and at least one of the following signs: cough or coryza or conjunctivitis, is a clinical case of measles.
Complications
Most measles cases experience at least one complication: Respiratory and ENT: pneumonia, otitis media, laryngotracheobronchitis Ocular: purulent conjunctivitis, keratitis, xerophthalmia (risk of blindness) Gastrointestinal: diarrhoea with or without dehydration, benign or severe stomatitis Neurological: febrile seizures; rarely, encephalitis Acute malnutrition, provoked or aggravated by measles (post-measles period) Pneumonia and dehydration are the most common immediate causes of death.
189
Measles
Case management
Treat as outpatient children with no major complications, no complications or minor complications: Pneumonia without severe signs Acute otitis media Purulent conjunctivitis (no corneal lesions) Diarrhoea without dehydration Oral candidiasis that does not interfere with eating If in doubt, keep the child under observation for a few hours. Isolation Isolation of hospitalised patients Measles cases treated as out-patients should be kept at home during this period.
Admit as inpatient children with at least one major complication: Inability to eat/drink/suck, or vomiting Altered consciousness or seizures Dehydration Severe pneumonia (pneumonia with respiratory distress or cyanosis or O2 sat. < 90%) Acute laryngotracheobronchitis (croup)1 Corneal lesions (pain, photophobia, erosion or opacity) Severe oral lesions that prevent eating Acute malnutrition
Treatment
Supportive and preventive treatment Treat fever (paracetamol, page 26). Make the child drink (high risk of dehydration). Give smaller, more frequent meals or breastfeed more frequently (every 2 to 3 hours). Clear the nasopharynx (nose-blowing or nasal lavages) to prevent secondary respiratory infection and improve the childs comfort. Clean the eyes with clean water 2 times daily and administer retinol on D1 and D2 (see page 122) to prevent ocular complications. In children under 5 years: amoxicillin PO for 5 days as a preventive measure (reduction of respiratory and ocular infections). In the event of watery diarrhoea without dehydration: oral rehydration according to WHO Plan A. Insert a nasogastric tube for a few days if oral lesions prevent the child from drinking. Treatment of complications See following page
1 Symptoms (hoarse crying or voice, difficulty breathing, a high-pitched inspiratory wheeze [inspiratory stridor],
characteristic "barking" cough) are caused by inflammation and narrowing of the larynx. Croup is considered benign or moderate if the stridor occurs when the child is agitated or crying, but disappears when the child is calm. The child should be monitored during this period, however, because his general and respiratory status can deteriorate rapidly. Croup is severe when the stridor persists at rest or is associated with signs of respiratory distress.
190
8. Viral diseases
Severe pneumonia
ceftriaxone IV or IM + cloxacillin IV then change to amoxicillin/clavulanic acid PO (see pages 68-69) + oxygen if cyanosis or O2 saturation < 90% + salbutamol if expiratory wheezing and sibilant rales on auscultation
Treatment of complications
Acute otitis media Dehydration Oral candidiasis Purulent conjunctivitis Keratitis/ keratoconjunctivitis Xerophthalmia Febrile seizures
For severe croup: dexamethasone IM: 0.6 mg/kg single dose + nebulized epinephrine (adrenaline, 1 mg/ml ampoule): 0.5 ml/kg (max. 5 ml) + oxygen if cyanosis or O2 saturation < 90% Intensive monitoring until symptoms resolve. See page 57 See page 92 Rehydration according to WHO Plan B or C. See page 123
Inpatient monitoring (risk of worsening). Keep the child calm. Agitation and crying exacerbate the symptoms.
for 5 days
tetracycline 1% eye ointment 2 times daily for 7 days + retinol PO one dose on D1, D2 and D8 (see page 121) + eye protection and tramadol PO from 6 months of age
No topical corticosteroids.
8
Prevention
No chemoprophylaxis for contacts. Vaccination: The first dose is administered at 9 months of age. In situations where there is high risk of infection (overcrowding, epidemics, malnutrition, infants born to a mother with HIV infection, etc.): administer one dose at 6 months of age (between 6 and 8 months) and one dose at 9 months of age, with an interval of at least 4 weeks between injections. Children must receive a second dose before they are 5 years old in order to cover unvaccinated children or children who did not respond to the first dose.
191
Poliomyelitis
Poliomyelitis
Poliomyelitis is an acute viral infection due to a poliovirus (serotypes 1, 2 and 3). Human-to-human transmission is direct (faecal-oral) or indirect (ingestion of food and water contaminated by stool). Humans are the only reservoir of the virus. In principle the disease can be eradicated by mass vaccination with oral polio vaccine (OPV). In endemic areas, epidemics usually affect children under 5 years of age. In nonendemic areas, where vaccination coverage is low, young adults are most commonly affected.
Clinical features
Non-paralytic form: a non-specific febrile illness with muscle pain, headache, vomiting, backache; no neurological involvement. As spontaneous recovery usually occurs within 10 days, diagnosis is rarely made outside epidemic contexts.
Paralytic form : in less than 1% of cases, after the non-specific signs, the patient develops rapid onset (from the morning to the evening) asymmetrical acute flaccid paralysis, predominantly of the lower limbs, with ascending progression. The muscles become soft with diminished reflexes. Sensation is maintained. The disease is life threatening if paralysis involves the respiratory muscles or muscles of swallowing. Initial urinary retention is common. Gastrointestinal disturbances (nausea, vomiting, diarrhoea), muscle pain and meningeal symptoms may also occur.
Laboratory
Look for the polio virus in stool samples. The virus is excreted for one month after infection, but only intermittently; therefore, 2 samples must be collected with an interval of 48 hours.
Treatment
Hospitalise patients with the paralytic form: rest, prevent bed sores in bedridden patients, give analgesics (do not give IM injections to patients in the febrile phase), ventilate patients with respiratory paralysis. Physiotherapy once the lesions are stable to prevent muscle atrophy and contractures. Care for sequelae: physiotherapy, surgery and prosthetics.
192
8. Viral diseases
Confirm the diagnosis by isolating the virus: send the 2 stool samples to a reference laboratory, with a clinical description of the patient. The stool samples must be stored and transported between 0C and 8C. Once the case is confirmed, organize a mass vaccination campaign: the area and the age group are determined as a function of epidemiological data. Surveillance: for each case of AFP there are between 100 and 200 subclinical cases. Therefore, active surveillance to detect new cases is essential for epidemic control.
While waiting for laboratory confirmation, vaccinate all children under 5 years of age living in the area (from the same village or neighbouring villages), irrespective of their vaccination status.
Prevention
2 types of vaccines exist: an injectable inactivated poliovirus vaccine (IPV) a trivalent oral attenuated poliovirus vaccine (OPV) In developing countries and during poliomyelitis eradication campaigns, the OPV is recommended for economic reasons, ease of administration and particularly for epidemiological reasons: it induces a rapid intestinal immunity (epidemic) and group protection due to its secondary diffusion into the natural environment Vaccination schedule with OPV The WHO recommends 4 doses before 1 year of age: Birth
Primary vaccination
10 weeks 14 weeks
6 weeks
Booster doses
One year after the last dose and at the age of 6 years
* If the first dose (OPV-0) is not administered at birth, give the 4th dose a minimum of 1 month after the 3rd dose, for example at the same time as measles vaccination.
193
Rabies
Rabies
Rabies is a viral infection of wild and domestic mammals, transmitted to humans by the saliva of infected animals through bites, scratches or licks on broken skin or mucous membranes. Any mammal can transmit rabies, but the great majority of human cases are due to dog bites. Once symptoms develop, rabies presents as a fatal encephalitis. There is no curative treatment; care is palliative. Before symptomatic disease has developed, rabies can effectively be prevented by postexposure prophylaxis.
Clinical features
The incubation period averages 20 to 90 days from exposure (75% of patients), but can be shorter (in severe exposure, i.e. bites to face, head and hands, multiple bites), or longer (20% of patients develop symptoms between 90 days and 1 year, and 5% more than 1 year after exposure). Prodromal phase: itching or paraesthesiae around the site of exposure, and nonspecific symptoms (malaise, fever, etc.). Neurologic phase: Furious form: psychomotor agitation or hydrophobia (throat spasms and panic, triggered by attempting to drink or sight/sound/touch of water) and aerophobia (similar response to a draft of air); sometimes seizures. The patient is calm and lucid between episodes. Paralytic form (less common, 20% of cases): progressive ascending paralysis resembling Guillain-Barr syndrome. Diagnosis is often difficult: there may be no history of scratch or bite (exposure through licking) or wounds may have healed; a reliable history may be difficult to obtain.
Post-exposure prophylaxis Risk of rabies virus infection: definition of exposure categories (WHO)
Category I Category II Nibbles on exposed skin Minor bite(s) or scratch(es) without bleeding Contact with animal, or licks on intact skin No exposure Minor exposure
Category III
Transdermal bite(s) or scratch(es) Licks on broken skin Contamination of mucous membranes by animals saliva (licks) Exposure to bat1
Severe exposure
194
8. Viral diseases
According to condition/type of wound In order to avoid inoculating virus deeper into the tissues, wounds are either not sutured at all (e.g. superficial, non-mutilating or puncture wounds), or are left open and re-evaluated in 48-72 hours, with a view to possible closure. Highly contaminated wounds, or wounds that may compromise function, require surgical management (exploration, removal of foreign material, excision of necrotic tissue, copious irrigation with 0.9% sodium chloride or Ringer lactate, with local or general anaesthesia). When suturing is unavoidable, rabies immune globulin should be administered several hours or days before wound closure (see below). Infected wounds are not sutured and reassessed daily.
In all cases Prolonged cleansing of the wound or contact site to eliminate the virus, as soon as possible after exposure, is of critical importance. For skin: use soap, rinse copiously with running water, remove all foreign material; application of polyvidone iodine 10% or ethanol 70% is an additional precaution which does not take the place of wound washing. For mucous membranes (eye, mouth, etc.): rinse thoroughly with water or 0.9% sodium chloride. Local cleansing is indicated even if the patient presents late.
Given the variable duration of incubation, administration of vaccine/immune globulin is an urgent priority, even for patients exposed several months previously.
Administration of rabies immune globulin Rabies immune globulin (RIG) is indicated for Category III exposures2, and Category II and III exposures in immune-compromised patients. RIG is intended to neutralize virus in the exposure site. It is given as a single dose on D0, with the first dose of rabies vaccine. Children and adults: human rabies immune globulin, 20 IU/kg, or highly purified equine immune globulin derivative F(ab)2, 40 IU/kg. Infiltrate as much of the dose as possible in and around the wounds(s)3. Inject any residual product, using the IM route, in a site remote from that used for vaccination. In the event of multiple wounds, dilute the dose 2- to 3-fold with sterile 0.9% sodium chloride to obtain a sufficient quantity to infiltrate all the sites exposed. If RIG is not available on D0, the first dose of rabies vaccine is administered alone. RIG can still be given as soon as possible within the next few days. However, RIG is no longer recommended when 7 or more days have elapsed since the first dose of vaccine was given, as vaccine-induced immunity will have developed by this time.
2 Unless it can be established that the patient has been correctly vaccinated against rabies before exposure
3 Infiltrate RIG, even if the wound has healed. For finger wounds, infiltrate very cautiously to avoid causing a
compartment syndrome. When it is not possible to infiltrate the wound (mucous membranes), the entire dose is administered IM. 195
Rabies
Post-exposure rabies vaccination A complete rabies vaccination series is indicated for Category II and III exposures. It should be started on D0 and continued to completion if the risk of rabies has not been excluded4. Several different types of rabies vaccine are available. Vaccines prepared from cell culture (CCV), e.g. human diploid cells (HDCV), Vero cells (PVRV) or chick embryo cells (PCECV) must replace nerve tissue vaccines (NTV). There are several possible vaccination protocols: check and follow national recommendations. The shortest regimens among those endorsed by the WHO are shown as examples:
No pre-exposure vaccination or Unknown vaccination status or Incomplete pre-exposure vaccination or Complete pre-exposure vaccination with a NTV Intramuscular (IM) 2-0-1-1
Administer in the deltoid Use only PVRV or PCECV muscle (anterolateral thigh in vaccine children < 2 years), never in the gluteal muscle One IM dose = 0.5 or 1 ml (depending on the manufacturer) One ID dose = 0.1 ml 2 doses (1 dose in each arm) 2 doses (1 dose in each arm) 2 doses (1 dose in each arm) 2 doses (1 dose in each arm)
D0 D3 D7 D21 D28
2 doses (one dose in each arm or thigh) 1 dose (in the arm or thigh) 1 dose (in the arm or thigh)
One IM dose = 0.5 or 1 ml (depending on the manufacturer) One ID dose = 0.1 ml 1 dose 1 dose
* Incorrect ID technique results in failure of PEP: if correct ID technique cannot be assured, use the IM regimen.
4 Either through observation of the captured animal (if domestic) or through laboratory diagnosis of the animal
No RIG
(killed). The WHO recommends a 10-day observation period of the animal, if captured. If no signs of rabies develop during the observation period, the risk of rabies is excluded, and rabies vaccination is discontinued. Laboratory diagnosis of the dead animal involves sending the head to a specialised laboratory, which confirms or excludes rabies in the animal. If laboratory diagnosis is negative, risk of rabies is excluded, and rabies vaccination is discontinued.
196
8. Viral diseases
Other measures
Tetanus vaccination and immune globulin Verify vaccination status. If unknown or not up-to-date, see page 170.
Antibiotic therapy or prophylaxis A 7-day course of antibiotics is indicated for infected wounds (redness, oedema, purulent or serosanguinous drainage, localised cellulitis, lymphangitis, lymphadenopathy, fever). A longer treatment and/or the parenteral route may be indicated in severe infection. Antibiotic prophylaxis (5 to 7 days) is recommended for deep puncture wounds, wounds on the face or hands, wounds involving joints, tendons, ligaments or fractures; very contaminated wounds or those requiring debridement; in immunecompromised patients. Antibiotic prophylaxis is not recommended for superficial wounds or wounds more than 24-48 hours old in patients showing no local or general signs of infection. The same dosage is used for both treatment and prophylaxis: amoxicillin/clavulanic acid (co-amoxiclav) PO5 (dosage expressed in amoxicillin): - Children < 40 kg: 45 to 50 mg/kg/day in 2 divided doses (if using ratio 8:1 or 7:1) or in 3 divided doses (if using ratio 4:1) The dose of clavulanic acid should not exceed 12.5 mg/kg/day or 375 mg/day. - Children 40 kg and adults: 1500 to 2000 mg/day depending on the formulation available: Ratio 8:1: 2000 mg/day = 2 tablets of 500/62.5 mg 2 times per day Ratio 7:1: 1750 mg/day = 1 tablet of 875/125 mg 2 times per day Ratio 4:1: 1500 mg/day = 1 tablet of 500/125 mg 3 times per day The dose of clavulanic acid should not exceed 375 mg/day.
5 Co-amoxiclav is the antibiotic of choice. Doxycycline (200 mg/day in 2 divided doses) may be used in penicillin-
197
Viral hepatitis
Viral hepatitis
Several viral infections of the liver are grouped under the heading of viral hepatitis: hepatitis A, B, C, (delta) and E. The different hepatitis viruses are present throughout the world, but their prevalence varies by country. Hepatitis A and B are common in developing countries where nearly the entire population is infected during childhood or adolescence. The clinical characteristics of all five diseases are similar enough to make differential diagnosis difficult; however, there are epidemiological, immunological and pathological differences. Patients with hepatitis B, C and may later develop chronic liver disease or even hepatocellular carcinoma. The main characteristics of each type of viral hepatitis are summarized in a table on the next page.
Clinical features
Asymptomatic forms Mild or anicteric forms are the most common, irrespective of the causal virus. The risk of developing later complications from hepatitis B, C and are the same as for symptomatic patients.
Classic forms Insidious or sudden onset with symptoms of varying intensity: fever, fatigue, nausea, gastrointestinal disturbance, followed by jaundice, dark coloured urine and more or less clay-coloured stool.
Fulminant forms Hepatocellular failure with severe, often fatal, cytolysis. This form is most frequent in hepatitis B patients with secondary infection with the virus, and in pregnant women infected with hepatitis E during their third trimester (20% mortality). Chronic hepatitis Hepatitis B, C and may lead to cirrhosis or hepatoma.
Ag HBs +/ + +
+/ +
Acute hepatitis
Interpretation
+/
Age group most at risk Children Blood and blood products Sexual Material contaminated with blood Vertical (mother-to-child) 2 to 25 weeks Co-infection B/: as for hepatitis B Secondary infection of hepatitis B: approximately 5 weeks Precedes signs. Duration is not well known, probably the same as for hepatitis B. 2 to 8 weeks Blood and blood products Sexual: low Material contaminated with blood (low) Probably vertical
Hepatitis B
Hepatitis C
Hepatitis
Hepatitis E
Transmission
Faecal-oral Contaminated food and water Transfusion (rare) 4 to 30 weeks (average 10 weeks)
Incubation period
2 to 6 weeks
Blood and blood products Faecal-oral Sexual Contaminated food and Material contaminated with water blood Possibly vertical
Period of communicability
Precedes signs. Precedes signs and lasts Brief: < 10 days after the entire active period. Can appearance of jaundice persist in chronic carriers. Most infectious at the end of incubation period. 1 to 3% More rare than in hepatitis B
Fulminant forms
0.2 to 0.4%
Precedes signs. Duration is not well known, probably the same as for hepatitis B. Could persist beyond normalisation of transaminases.
Precedes signs. Duration is not well known (10 to 15 days after the appearance of jaundice)
Prognosis
No chronic forms
Chronicity: 0.2 to 10% of which 5 to 15% progress to cirrhosis. Hepatoma possible Specific anti-HBs immunoglobulin Safe sex (condoms) Anti-hepatitis B
Chronicity: up to 50%, of which 10 to 25% progress to cirrhosis. Hepatoma possible Specific anti-HBs immunoglobulin may be effective
Much more common in 20% mortality in pregnant patients with secondary women infection of hepatitis B than in patients with B/ co-infection Chronicity: 2 to 5% for No chronic forms patients with B/ coinfection; > 90% if secondary infection of hepatitis B (rapid cirrhosis)
Individual prevention
Polyvalent immunoglobulin
Vaccination
8. Viral diseases
Anti-hepatitis A
Anti-hepatitis B
Limit transfusion, screen blood prior to transfusion Single use of disposable material
Hygiene, sanitation
199
Viral hepatitis
Treatment
Rest, hydration, no special diet. Drug therapy for symptomatic treatment (analgesics, antipyretics, antidiarrhoeals, antiemetics etc.) during the acute phase is contra-indicated as it may aggravate symptoms and the evolution of hepatitis. Corticosteroids are not indicated.
Vaccination
Only against hepatitis A and B. Vaccination against hepatitis B is included in the EPI of some countries. IM vaccination against hepatitis B: Standard schedule Newborns, infants In countries where perinatal infection is common: one injection after birth, then at 6 and 14 weeks Where perinatal infection is less common: one injection at 6, 10 and 14 weeks Children, adolescents, adults Schedule 0-1-6: 2 injections 4 weeks apart, then a 3rd injection 5 months after the 2nd injection Accelerated schedule, when rapid protection is required (imminent departure in highly endemic areas, post-exposure prophylaxis) Schedule D0-D7-D21: 3 injections administered during the same month, then a 4th injection one year after the 1st injection
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Dengue fever
Dengue fever is an arthropod-borne viral disease transmitted to man through the bite of the Aedes mosquito. It develops sporadically and/or as epidemics (southeast Asia, the Pacific, Africa, the Caribbean and South and Central America). Four different serotypes of dengue virus exist. Primary infection with the dengue virus may be asymptomatic or may present as classical dengue fever. A second infection with a different serotype may provoke dengue haemorrhagic fever, characterised by an increased vascular permeability with loss of plasma from the vascular compartment and haemoconcentration. Dengue haemorrhagic fever may progress to dengue shock syndrome if, at the end of the febrile period, a significant plasma loss is not well compensated.
Clinical features
Dengue fever fever with headache, retro-orbital pain, muscle and joint pain maculopapular rash on the lower limbs common and benign haemorrhagic signs: skin (petechiae or positive tourniquet test1) and more rarely, mucosal (epistaxis, gingival bleeding)
Dengue shock syndrome The critical stage is at the end of the febrile period (from Day 3 to Day 7). The signs preceding shock are: persistent vomiting, intense abdominal pain, agitation or lethargy, sudden hypothermia. Ascites or pleural effusion are possible. Signs of shock: rapid and weak, then undetectable pulse cold extremities, profuse sweating narrow pulse pressure, hypotension Grading severity of dengue haemorrhagic fever (from WHO)
Clinical features Grade II I Fever + non-specific general symptoms + haemorrhagic signs (positive tourniquet test1 and/or easy bruising) Grade I manifestations + spontaneous bleeding (skin or other haemorrhages) Circulatory failure Profound shock with undetectable pulse and blood pressure
Dengue haemorrhagic fever high fever (39C-41C) of sudden onset lasting 2 to 7 days (sometimes with 2 peaks) haemorrhagic signs: skin (petechiae, purpura, ecchymoses, positive tourniquet test1); mucous membranes (epistaxis, gingival bleeding); gastrointestinal tract (haematemesis, melaena); bleeding from venepuncture sites hepatomegaly
1 Tourniquet test: inflate a blood pressure cuff on the upper arm to a point midway between the systolic and diastolic
IV
III
pressure for 5 minutes. The test is considered positive when 20 or more petechiae per 2.5 cm square are observed.
201
Dengue fever
Laboratory
Complete blood count (CBC) and differentials with platelet count: leukopenia and thrombocytopenia are common with 100 000 platelets/mm3.
Haematocrit is the only test that shows haemoconcentration and therefore differentiates dengue fever from dengue haemorrhagic fever (haematocrit elevated 20% above average for the age and sex: e.g. if the average haematocrit for the relevant population is 35%, a haematocrit of 42% corresponds to an increase of 20%).
Confirmation of the diagnosis: Confirm the aetiology at the beginning of an epidemic with serology (ELISA or rapid tests): elevated IgG and IgM anti-dengue antibodies confirm a recent infection. The IgM/IgG ratio differentiates primary infection (high ratio) from a secondary infection (low ratio), and therefore risk of shock. An increase in antibodies between two samples (from the beginning and end of an episode) confirms an acute infection. The serotype is identified by serology or PCR.
Treatment
Dengue haemorrhagic fever (Grades I and II) Hospitalise and observe children under 15 years, patients presenting with significant or repeated haemorrhages, patients with less than 20 000 platelets/mm3 and all patients having difficulty eating or drinking. Monitor vital signs (pulse, blood pressure, respiratory rate and urine output) every 3 hours and haematocrit every 6 hours. Look for the signs that precede shock. Administer Ringer Lactate: 7 ml/kg/hour for 6 hours then adapt according to the clinical evolution and haematocrit. If there is an improvement: progressively reduce the rate to 5 ml/kg/hour then 3 ml/kg/hour and stop the infusion after 24 to 48 hours. If there is no improvement: increase to 10 ml/kg/hour, then 15 ml/kg/hour. Place the patient under a mosquito net. IM injections are contra-indicated.
Dengue fever Give paracetamol PO (see Fever , page 26); wrap the patient in a wet cloth. Acetylsalicylic acid (aspirin) is strictly contra-indicated. Prevent or treat moderate dehydration (plenty of fluids, oral rehydration salts, follow Treatment plans A or B to treat dehydration, WHO, pages 316 to 320).
Dengue shock syndrome: emergency +++ (Grades III and IV) Administer Ringer Lactate: 10 to 20 ml/kg in less than 20 minutes, to be repeated if necessary, until a cumulative volume of 30 ml/kg is reached. If vital signs and haematocrit improve: change to 10 ml/kg/hour and then adapt accordingly. If there are no signs of improvement: administer oxygen and immediately check haematocrit: if the haematocrit is still elevated or has risen: plasma substitute 10 to 20 ml/kg infused in less than 10 minutes. Repeat if necessary, until a cumulative volume of 30 ml/kg is reached, then give 10 to 20 ml/kg/hour until improvement in the vital signs is seen.
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8. Viral diseases
Continue to monitor vital signs every 15 to 30 minutes and check haematocrit every 2 hours for the first 6 hours then every 4 hours. Monitor closely for the following 48 hours as shock may recur.
a sudden drop in haematocrit without clinical improvement is a sign of haemorrhage (often gastrointestinal or internal): transfuse fresh blood, 10 to 20 ml/kg (ensure screening for HIV, hepatitis B and C etc.).
Warning: monitor for fluid overload. Puffy eyelids are the first sign of fluid overload. Stop the infusion until the puffiness disappears. In the event of pulmonary oedema (laryngeal crackles, dyspnoea, increased respiratory rate, cough with or without frothy expectorant, anxiety, crepitations in both lung fields or tachycardia), give: furosemide IV, to be repeated after 1 to 2 hours if necessary: Children: 1 mg/kg/injection Adults: 40 mg/injection In an infant with a febrile seizure: see Seizures, page 23.
Stop the infusions once the vital signs are normal and stable, the patient has regained appetite and the haematocrit is normalised, usually 48 hours after shock.
Prevention
In endemic areas an epidemic risk exists: report probable or confirmed cases. Individual protection: mosquito nets and repellents. Vector control is essential, particularly during epidemics: destruction of larval habitats, insecticide spraying.
203
Clinical features
Common syndrome (CS): fever higher than 38.5C short remission on Day 3 or Day 4 haemorrhagic symptoms (purpura, epistaxis, haematemesis, melaena etc.) The clinical signs are often non-specific, the severity varies depending on the aetiology (see table, page 206). Send a sample of whole blood to a reference laboratory (eg. the Pasteur Institute) for serological diagnosis. Attach a clinical description of the patient. Wear protective clothing while taking or handling the sample (gloves, protective glasses etc.). Use a triple packaging system for shipment. The tube containing the blood specimen is placed in a primary watertight, rigid container enclosing absorbent material between it and the tube containing the blood specimen (1). There must be enough absorbent material to soak up the entire blood sample in the event of a leak. This primary container is then placed in a second rigid container appropriately sealed for transport of infectious materials (2). This second container is placed in a secure carton box that has a visible infectious substance (biohazard) label (3). The sample may also be sent on filter paper. It is easier to transport, but the small volume of blood only allows a limited number of aetiologies to be tested.
Laboratory
Management
Suspicion of haemorrhagic fever (isolated case of fever with haemorrhagic symptoms in an endemic area): Isolation: isolation ward (or failing that screens/partitions); restrict visitors (provide protective clothing: gowns, gloves, masks). Standard precautions: The general rules of hygiene must always be respected. The majority of intra-hospital infections have occurred due to a lack of respect for these simple rules. wear gloves for taking samples wear gowns during consultations and care wear thick rubber gloves to handle soiled laundry frequent hand washing respect safe injection practices In addition to these non-specific measures wear masks and gloves while examining the patient and protective glasses when there is a risk of splashing. Confirmed cases of Ebola, Marburg, Lassa, Crimean-Congo haemorrhagic fevers or epidemics of unknown origin: More specific measures: strict isolation in a reserved area separate from other patient areas, with a changing room at the entrance/exit
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disinfection (2% active chlorine), and safe disposal of excreta disinfection of contaminated laundry in chlorine solution (0.1% active chlorine) protective clothing for staff: double gloves, mask, cap, protective glasses, double gown, apron, rubber boots entry/exit: clean laundry for staff at entry; disinfection station at the exit. Gowns, boots and rubber gloves are soaked in a chlorine solution (0.1% active chlorine) for 2 hours before cleaning. Containers for the safe disposal of disposable material. Hand washing with soap. The caregiver (maximum one per patient), helped and supervised by the medical staff, follows the same protective measures. In the event of a death, do not wash the body. If it is imperative for cultural reasons: wear protective clothing, wash the body with chlorinated water (2% active chlorine), and restrict the number of people involved. Bury the body as quickly as possible, using a body bag when feasible. Wear protective clothing when handling contaminated material. No contaminated material should leave the isolation area which includes an incinerator, a sharps pit and a biological waste pit. Confirmed cases of Yellow fever or Rift Valley fever: Standard precautions Keep the patient under a mosquito net to prevent transmission For all patients: report to the Ministry of Health of the country
Aetiological treatment: only for Lassa fever and Crimean-Congo fever (ribavirine). Symptomatic treatment: fever: paracetamol (see Fever, page 26). Acetylsalicylic acid (aspirin) is contraindicated. pain: mild (paracetamol), moderate (tramadol), severe (sublingual morphine): see Pain, page 29. dehydration: follow Treatment plans A, B or C to treat dehydration, WHO, pages 316 to 321. haemorrhagic shock: see page 19 seizures: see page 23 vomiting: promethazine PO Children from 2 to 10 years: 10 to 25 mg to be repeated every 6 hours if necessary Children over 10 years and adults: 25 mg to be repeated every 6 hours if necessary For Ebola and Marburg haemorrhagic fevers: invasive procedures must be strictly limited. Health care staff are at risk of contamination when inserting and maintaining intravenous lines. An intravenous line must be well secured so that the patient, often confused, cannot pull it out.
Treatment
Prevention
Vaccination Yellow fever: Mass vaccination campaign during an epidemic Children from 6 months and adults: a single dose of 0.5 ml IM (preferred) or deep SC, in the deltoid muscle. In pregnant women, only administer during an epidemic. Routine vaccination (EPI) Rift Valley fever (only during an epidemic) Vector control programmes for known vectors. Hospital hygiene measures are essential in all cases.
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206
Ebola* Marburg Strict isolation - periorbital oedema, cervical adenopathy, pharyngitis - pharyngitis, reddened conjunctivae CS + vomiting, erythema of the face and, depending on the aetiology: CS + facial oedema, purulent pharyngitis, proteinuria on reagent strip (10-25%) (60-80%)
Reservoir/ Vector Geographical distribution Strict isolation CS + sudden onset general malaise, vomiting and diarrhoea (estimated case fatality rate)
Unknown Africa
Isolation of patients
Clinical feataures
Omsk
Crimean Congo*
Kyasanur
Livestock/Mosquitoes Africa
Yellow fever*
(30-50%)
8. Viral diseases
Primary infection or acute retroviral syndrome: 50 to 70% of newly infected individuals develop a viral syndrome (fever, malaise, lymphadenopathy) during seroconversion (from 15 days to 3 months post exposure). Asymptomatic HIV infection (after seroconversion): a period of clinical latency, but not viral latency. The time period for progression from HIV infection to the development of severe immune deficiency in western countries is 10 years. This period appears to be shorter in developing countries. Symptomatic HIV infection : with progressive destruction of the immune system, common and more severe diseases occur more frequently, and with higher mortality, in seropositive individuals.
AIDS: this stage corresponds to the development of severe opportunistic infections and neoplasms. From a biological point of view, AIDS is defined as a CD4 count below 200 cells/mm3. Without treatment the disease progresses rapidly towards death.
Unexplained severe weight loss (> 10% of presumed or measured body weight) Unexplained chronic diarrhoea for longer than one month Unexplained persistent fever (> 37.5C intermittent or constant for > 1 month) Persistent oral candidiasis Oral hairy leukoplakia Pulmonary tuberculosis Severe bacterial infections (e.g. pneumonia, empyema, pyomyositis, bone or joint infection, meningitis, bacteraemia) Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Unexplained anaemia (< 8 g/dl), neutropenia (< 0.5 x 10 9 /L) and/or chronic thrombocytopenia (< 50 x 109/L3) Clinical stage 4 HIV wasting syndrome Pneumocystis pneumonia Recurrent severe bacterial pneumonia Chronic herpes simplex infection (orolabial, genital or anorectal of more than one months duration or visceral at any site) Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs) Extrapulmonary tuberculosis Kaposis sarcoma Cytomegalovirus infection (retinitis or infection of other organs) Central nervous system toxoplasmosis HIV encephalopathy Extrapulmonary cryptococcosis including meningitis Disseminated nontuberculous mycobacteria infection Progressive multifocal leukoencephalopathy Chronic cryptosporidiosis Chronic isosporiasis Disseminated mycosis (extrapulmonary histoplasmosis, coccidiomycosis) Recurrent septicaemia (including nontyphoidal Salmonella) Lymphoma (cerebral or B-cell non-Hodgkin) Invasive cervical carcinoma Atypical disseminated leishmaniasis Symptomatic HIV-associated nephropathy or cardiomyopathy Note: this classification is only for adults and adolescents. Another four-stage clinical staging has been developed for children.
Clinical stage 3
Laboratory
Diagnosis of HIV infection The diagnosis of HIV infection is made with serological testing. Testing is done voluntarily with informed consent. Testing is never mandatory. Every individual has the right to know or not to know his HIV status. Test results are confidential to avoid discrimination. The individual should have access to minimum services offering pre-test and post-test counselling, treatment and support.
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A positive diagnosis is made when at least 2 different tests (2 different brands) are both clearly positive. A first negative test should be repeated 3 months later to exclude seroconversion (window period). CD4 cell depletion is a marker of the progression of immune depression. It is a predictor of the development of opportunistic infections or neoplasms and can be used to orient their diagnosis (e.g. cerebral toxoplasmosis or cryptococcal meningitis appear when the CD4 count is below 100 cells/mm3. If clinical signs indicating these infections are present, but the CD4 count is greater than or equal to 200 cells/mm3, it is unlikely that these infections are present). The CD4 cell count is also used as an indicator for primary prophylaxis (see primary prophylaxis, page 211) and initiation of ARV treatment. CD4 lymphocyte counts
Therapeutic classes Three major classes of ARV exist: NRTI (nucleoside/nucleotide reverse transcriptase inhibitors): zidovudine (AZT), lamivudine (3TC), didanosine (ddI), stavudine (d4T), abacavir (ABC), tenofovir (TDF), emtricitabine (FTC). NNRTI (non-nucleoside reverse transcriptase inhibitors): efavirenz (EFV), nevirapine (NVP). HIV-2 is naturally resistant to NNRTI. PI (protease inhibitors): indinavir (IDV), lopinavir (LPV), ritonavir (RTV), saquinavir (SQV). Principles of ARV treatment Daily triple therapy must be taken for life to prevent the rapid development of resistance. It is important that the patient understands this and that adherence to treatment is optimal. The most widely-used and easiest regimens to administer are 2 NRTI + 1 NNRTI: e.g. d4T + 3TC associated with NVP or EFV (EFV is contra-indicated in pregnant women). In the event of treatment failure, use as a second-line: 2 other NRTI + 1 PI. Other possible combinations exist which are less commonly used or more difficult to manage.
Criteria for ARV treatment As there are large numbers of patients who would benefit from treatment, it seems legitimate to prioritise the treatment of patients already in clinical stage 3 and 4 and patients most at risk of developing severe opportunistic infections (patients with a CD4 count below 200 cells/mm3).
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Monitoring of ARV treatment CD4 counts are useful in the initiation and follow-up of treatment. CBC, haemoglobin and ALAT are not essential, but can be useful in detecting treatment adverse effects. Viral load (rarely available) is useful for detection of treatment failures. Treatment of opportunistic and other infections With progressive immunosuppression, HIV infected patients who are not receiving triple therapy (or patients with poor adherence) become increasingly susceptible to infections. For conditions of clinical stages 2 and 3, standard treatments are usually effective and the diagnosis of HIV infection does not much alter the clinical management. Patients in these stages may benefit from primary prophylaxis (see primary prophylaxis, page 211). Severe opportunistic infections often require sophisticated diagnostic and therapeutic means rarely available. However, with improving health services, most of these diseases can be treated. For treatment of opportunistic infections, see tables, pages 213 to 219. Treatment of pain Treat all patients for associated pain (see Pain, page 29).
Sexual transmission The only reliable method of prevention is the use of male or female condoms. In addition, early diagnosis and treatment of sexually transmitted infections is essential as they increase the transmission of HIV (see Chapter 9). Post-exposure prophylaxis (PEP): e.g. in the event of rape, ARV treatment begun within 48 hours after possible exposure and given for a duration of 1 month may reduce the risk of infection.
Occupational transmission (accidental needle stick injuries or injuries with contaminated objects, contact between a patients blood and unprotected broken skin or mucous membranes). Prevention is based on use of universal precautions to avoid contamination with soiled material or potentially infected body fluids. Post exposure prophylaxis (PEP): e.g. in the event of an accident, ARV treatment begun within 48 hours after the accident and given for a duration of 1 month reduces the risk of infection.
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Transmission through blood and blood products transfusion: strict respect of indications for transfusion and systematic serological screening of the donor s blood are the two indispensable precautions in the prevention of HIV transmission through transfusions. IV drug use: needle and syringe exchange programmes with disposable needles and syringes for users.
8. Viral diseases
Nosocomial transmission Prevention of nosocomial HIV infection is based on the rational use of injections and strict respect for hygiene and sterilisation and disinfection procedures for medical material. Mother-to-child transmission (MTCT) The global rate of vertical transmission varies from 20% to 40%. The risk of transmission through breastfeeding is evaluated at approximately 12% and persists for the duration of breastfeeding. In pregnant women: HIV transmission from mother-to-child may be reduced by the administration of ARVs. Many different protocols exist of varying complexity, duration and effectiveness. The most commonly used ARV are AZT, 3TC and NVP. ARV are administered to the mother during pregnancy, labour, post-partum period and to the newborn. Check national recommendations. Programmes targeting pregnant women also include other preventive measures: no systematic episiotomy; avoid artificial rupture of the membranes. In certain situations, where the context allows, an elective caesarean section (prior to commencement of labour or rupture of membranes), under antiretroviral cover, may reduce mother-to-child transmission. It is absolutely imperative to consider the risk of a caesarean section against the benefit of this intervention. In breastfeeding women : artificial milk if the supply of milk and safe water is guaranteed. If not, exclusive maternal breastfeeding until the age of six months followed by weaning over 1 month period. Mixed feeding (maternal + artificial milk) is contra-indicated.
In the absence of ARV treatment, all HIV infections become symptomatic and evolve towards AIDS. However, some opportunistic infections can be prevented. Primary prophylaxis For HIV infected patients who have not previously contracted an opportunistic infection, in order to prevent the development of some opportunistic infections.
Criteria for primary prophylaxis: In the absence of CD4 count: WHO clinical stages 2, 3 and 4. If CD4 count is feasible: WHO clinical stages 3 and 4 irrespective of the CD4 count and WHO clinical stages 1 and 2 with CD4 count < 350 cells/mm 3 (or even 500 cells/mm3, depending on national recommendations).
Pneumocystosis Cerebral toxoplasmosis Isosporiasis Various bacterial infections Malaria
Infections
cotrimoxazole
PO: Children: 50 mg SMX + 10 mg TMP/kg once daily Adults: 800 mg SMX + 160 mg TMP once daily
Primary prophylaxis
211
Secondary prophylaxis
For patients who develop a specific opportunistic infection, in order to prevent recurrence once treatment for the infection is completed.
Pneumocystosis Toxoplasmosis
Infections
Secondary prophylaxis
Children: 50 mg SMX + 10 mg TMP/kg once daily Adults: 800 mg SMX + 160 mg TMP once daily
cotrimoxazole PO:
Isosporiasis
Alternatives: Adults: sulfadiazine PO: 2 g daily + pyrimethamine PO: 25 mg daily + folinic acid PO: 25 to 30 mg weekly or dapsone PO: 200 mg weekly or 50 mg daily + pyrimethamine PO: 75 mg weekly + folinic acid PO: 25 to 30 mg weekly
Alternative: dapsone PO Children: 2 mg/kg once daily without exceeding 100 mg/day Adults: 100 mg once daily
Comments
Penicilliosis Histoplasmosis
Cryptococcal meningitis
fluconazole PO: Children: 6 mg/kg once daily Adults: 200 mg once daily
itraconazole PO:
fluconazole PO: Children: 3 to 6 mg/kg once daily Adults: 100 to 200 mg once daily aciclovir PO:
Children under 2 years: 400 mg/day in 2 divided doses Children over 2 years and adults: 800 mg/day in 2 divided doses
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Symptoms
1. History and clinical examination 2. Microscopic examination of stool for ova and parasites (2 to 3 samples)
Diagnosis
Treatment
Parasitic infections Isospora belli Cryptosporidium Microsporidium Giardia lamblia Entamoeba histolytica
Aetiologies:
- Persistent (> 2 weeks) or chronic (> 4 weeks) diarrhoea is often associated with weight loss and dehydration. - Prevention or treatment of dehydration is critical (pages 316 to 321). - Depending on the results of the stool examinations: give appropriate treatment. - If there is no laboratory support:
Other causes Kaposis sarcoma Lymphoma Idiopathic (HIV infection) Antiretrovirals (especially lopinavir and ritonavir)
Acute bloody diarrhoea - First-line treatment: Note: Children: azithromycin PO: 20 mg/kg once daily for 5 days I. belli, Cryptosporidium, or ciprofloxacin PO: 30 mg/kg/day in 2 divided doses for 7 days Microsporidium, MAC and Adults: ciprofloxacin PO: 1 g/day in 2 divided doses for 7 days CMV are unlikely if - If amoebiasis suspected: tinidazole or metronidazole PO, see page 88 CD4 count > 200 cells. Non-bloody persistent or chronic diarrhea Persistent or chronic diarrhoea suggests advanced immunocompromised state. For patients who qualify for ARVs by CD4 count (or unknown CD4 count), ARV initiation is urgent and will usually resolve symptoms in 14 to 28 days. - Isospora belli: cotrimoxazole PO Children: 80 mg SMX + 16 mg TMP/kg/day in 2 divided doses for 10 days followed by 50 mg SMX + 10 mg TMP/kg/day in 2 divided doses for 3 weeks Adults: 1600 mg SMX + 320 mg TMP/day in 2 divided doses for 7 to 10 days followed by 800 mg SMX + 160 mg TMP/day in 2 divided doses for 3 weeks - Cryptosporidium: no specific treatment in HIV-infected patients - Microsporidium: albendazole PO (limited efficacy) Children: 20 mg/kg/day (max. 800 mg) in 2 divided doses for 7 days Adults: 800 mg/day in 2 divided doses for 2 to 4 weeks - Helminthiasis: albendazole PO Children > 6 months but 10 kg: 200 mg once daily for 3 days Children > 6 months and adults: 400 mg once daily for 3 days - Giardiasis: tinidazole or metronidazole, see page 147
- If no improvement (and no contra-indications such as bloody diarrhoea), symptomatic treatment with loperamide PO: Children < 2 years: contra-indicated Children 2 to 5 years: 3 mg/day Children 6 to 8 years: 4 mg/day Children > 8 years: 6 to 8 mg/day Adults: initial dose of 4 mg then 2 mg after each liquid stool (max. 16 mg/day)
8. Viral diseases
213
214
Symptoms
Diagnosis
Treatment
(continued)
Nutrition ++++ Children: continue to breastfeed; increase daily calorie intake: children 6-11 months: add 150 kcal/d children 12-23 months: add 200 kcal/d children 2-5 years: add 250 kcal/d children 6-9 years: add 350 kcal/d children 10-14 years: add 400 kcal/d Eliminate fresh milk, give porridge prepared with rice water or soup or yoghurts. Give 2.5 ml of oil/meal. Any child 0-5 years should receive zinc sulfate (see page 84). Adults: increase the calorie and protein intake (at least 2 g protein/kg/day). No food is excluded but avoid raw food, fresh milk and foods high in fibre. Encourage small, frequent meals. - Oral candidiasis: miconazole gum patch: apply one patch/day to the gums for 7 days or nystatin PO (100 000 IU/ml oral susp.): 4 ml 4 times daily for 14 days Note: oral candidiasis is an indication for PCP prophylaxis
Fungal infections Oral candidiasis: whitish plaques on the oral mucosa, difficult to detatch. If detatched: granulous and bloody base. Oesophageal candidiasis: pain on swallowing, dysphagia. May result in weight loss.
Viral infections Oral hairy leukoplakia (keratosis on the lateral sides of the tongue due to the Epstein-Barr virus) Oral and oesophageal herpes
Aphthous ulcers
- Oesophageal candidiasis: fluconazole PO for 14 to 21 days: Children: 3 a 6 mg/kg once daily Consider all severe oral Adults: 50 a 200 mg once daily candidiasis (if the pharynx These doses can be increased up to 400 mg/day if necessary. is involved) as oesophageal candidiasis even in the - Oral hairy leukoplakia: no treatment absence of dysphagia. - Oral herpes: Analgesics (paracetamol, ibuprofen) For recurrent or extensive forms affecting the oesophagus, add: aciclovir PO within the 96 hours following the onset of lesions: Children under 2 years: 200 mg 5 times/day for 7 days Children over 2 years and adults: 400 mg 5 times/day for 7 days Secondary prophylaxis only for patients with frequent recurrences
Symptoms
For the diagnosis and treatment of upper respiratory tract infections, particularly pneumonia: see Chapter 2
Diagnosis
Treatment
Respiratory problems
If the sputum examination is AFB+, treat for tuberculosis (no thioacetazone: risk of severe reactions in HIV infected patients)
If the chest x-ray is consistent with staphylococcal pneumonia: Children: see Staphylococcal pneumonia, page 73 Adults: ceftriaxone IM or slow IV 1 g/day once daily + cloxacillin IV 8 g/day in 4 divided doses
Cough and/or thoracic pain and/or 1. History and clinical dyspnoea in a symptomatic HIV examination: infected patient. Blood in the sputum? (also see chapter 2) If fever < 7 days, dyspnoea: Aetiologies: unlikely TB. If cough > 21 days, weight Bacterial infections loss, thoracic pain Pyogenic bacteria (Streptococcus > 15 days, no dyspnoea: pneumoniae, Haemophilus influenzae, likely TB. Staphylococcus aureus) Pulmonary auscultation: bilateral lobar pneumonia? Mycobacterial infections M. tuberculosis, MAC 2. If possible: a) Look for AFB in sputum Protozoal infections (2 samples) Pneumocystis jiroveci b) Chest x-ray Pneumocystis: bilateral Fungal infections interstitial infiltrates Cryptococcus neoformans, Tuberculosis: lobar Histoplasma capsulatum, consolidation, cavitation, Coccidioides immitis, Aspergillus spp, pleural effusion, intraPenicillium marneffei thoracic lymphadenopathy Warning: the classic Viral infections radiological signs of CMV tuberculosis are not always found in HIV + tuberculosis Neoplasms patients. Kaposis sarcoma Non-Hodgkins lymphoma Notes: MAC, pneumocystis, Others CMV and fungal infections Lymphoid interstitial pneumonia are unlikely in patients Pleural effusion (often TB) with a CD4 count Pericardial effusion (often TB) > 200 cells/mm3 Pneumothorax (may be due to Staphylococcal PCP) pneumonia is often associated with a pyomyositis or an abscess
Fungal infections (cryptococcosis, penicilliosis, histoplasmosis): Adults: amphotericin B IV: 0.7 to 1 mg/kg/day for 2 weeks (cryptococcosis, penicilliosis) or one to 2 weeks (histoplasmosis), then: fluconazole PO: 400 mg/day for 8 weeks (cryptococcosis) itraconazole PO: 400 mg/day in 2 divided doses for 10 weeks (penicilliosis) itraconazole PO: 600 mg/day in 3 divided doses for 3 days then 200 to 400 mg/day for 12 weeks (histoplasmosis) Secondary prophylaxis is recommended.
If the sputum examination is negative and the chest x-ray is consistent with Pneumocystis jiroveci pneumonia: cotrimoxazole PO for 21 days Children: 100 mg SMX + 20 mg TMP/kg/day in 2 divided doses Adults: 4800 SMX + 960 TMP/day in 3 divided doses Note: the symptoms may become worse during the first phase of treatment, effectiveness can only be evaluated after one week of treatment. In cotrimoxazole-allergic patients: Adults: clindamycin PO or IV: 2.4 g/day in 4 doses or injections + primaquine PO: 15 mg once daily for 21 days For either treatment, add prednisolone PO for patients with severe pneumocystosis with hypoxia: Children: start with 2 mg/kg/day then decrease the dose following the adult example Adults: 80 mg/day in 2 divided doses for 5 days, then 40 mg/day for 5 days then 20 mg/day for 10 days Secondary prophylaxis is recommended.
8. Viral diseases
215
216 1. Clinical examination: look for a local cause (skin or dental infection etc.); TB or syphilis. - Tuberculosis: see the MSF handbook Tuberculosis.
Symptoms
Diagnosis
- Treat according to the aetiology or empirical treatment with, for example cloxacillin or doxycycline PO.
Treatment
Persistent generalised lymphadenopathy (PGL): 2 or more extra-inguinal sites lymph nodes > 1.5 cm enlarged for 3 or more months PGL is usually due to HIV infection. 3. Suspected syphilis: serology, direct microscopy 4. If all examinations are negative: biopsy is useful to exclude lymphoma, Kaposis sarcoma and fungal or mycobacterial infections (see notes for patients in Stage 1).
2. Suspected TB: - Early syphilis: benzathine benzylpenicillin IM lymph node aspiration, look Adults: 2.4 MIU as a single dose (1.2 MIU in each buttock) for AFB, chest x-ray Note: in HIV infected patients, tuberculosis is often extraNote: in patients in Stage 1, no further investigation (other than 1, 2 and 3 in pulmonary. this table) or treatment are required.
Symptoms
Treatment
Bacterial infections Furunculosis (see also Chapter 4) Impetigo and pyoderma Axillary hidradenitis Pyomyositis Bacillary angiomatosis Syphilis
Skin lesions
Viral infections Herpes zoster Herpes simplex Genital warts Molluscum contagiosum
Bacterial infections: Furunculosis, impetigo, chronic folliculitis: local treatment, +/- cloxacillin PO: see Bacterial skin infections, Chapter 4. Suppurative axillary hidradenitis: local treatment + doxycycline PO: 200 mg/day in 1 or 2 divided doses for 6 weeks (in adults) Pyomyositis: antibiotics/surgical drainage, see Pyomyositis, Chapter 10. Bacillary angiomatosis: Adults: erythromycin PO 2 g/day in 2 or 3 divided doses for 2 months or doxycycline PO 200 mg/day in 2 divided doses for 2 months Primary and secondary syphilis: see Chapter 9. Viral infections: Herpes zoster: local treatment and analgesics, see Herpes simplex and herpes zoster, Chapter 4 For necrotic, extensive forms, eruption on the face, ophthalmic zoster, add aciclovir within 48 hours of the onset of lesions: Children (IV route): 15 to 30 mg/kg/day in 3 infusions (every 8 hours) for 7 days Adults (oral route): 800 mg 5 times daily for 7 days Herpes simplex: local treatment, see Herpes simplex and herpes zoster, Chapter 4. Genital warts: see Chapter 9.
Fungal infections Fungal infections: Candidiasis, dermatophytoses and Candidiasis: 2% cream miconazole, twice daily deep mycoses (penicilliosis, Dermatophytoses: see Superficial fungal infections, Chapter 4. cryptococcosis, histoplasmosis etc.)
Other skin infections Chronic prurigo or urticaria Severe seborrhoeic dermatitis Psoriasis Scabies Diffuse cutaneous xerosis
Other skin infections: Prurigo, urticaria: see Other skin disorders, Chapter 4. Seborrhoeic dermatitis: Whitfields ointment or ketoconazole or 2% miconazole applied twice daily. For severe inflammation, use a topical corticosteroid in combination with either miconazole or ketoconazole. Xerosis: zinc oxide ointment or calamine lotion Psoriasis: corticosteroides and zinc oxide ointment Scabies: local treatment. For crusted or profuse scabies, add ivermectin PO (see Scabies, Chapter 4).
8. Viral diseases
Bed sores
217
218
Symptoms
For patients with focal signs, treat for toxoplasmosis for 6 weeks: Positive thick and thin films: see Malaria, Chapter 6.
Headache and neurological disorders in adults 50 mg SMX + 10 mg TMP/kg/day in 2 divided doses for 4 weeks A secondary prophylaxis is recommended.
Aetiologies:
Persistent headache that does not respond to usual analgesics in a symptomatic HIV infected patient.
Diagnosis
Treatment
Infections Tuberculous meningitis Cryptococcal meningitis Cerebral toxoplasmosis Neurosyphilis CMV encephalitis HIV encephalopathy Progressive multifocal leukoencephalopathy Cerebral malaria
History and clinical examination: Change in mental state Focal deficits Seizures Signs of meningeal irritation Raised intercranial pressure Motor problems, ataxia
pyrimethamine PO: 200 mg in 2 divided doses on the 1st day, then 75 to 100 mg/day + sulfadiazine PO: 4 to 6 g/day + folinic acid PO: 15 mg/day or, failing that, cotrimoxazole PO at high doses:
Common causes of headache unrelated to HIV infection: sinusitis, problems with accommodation etc. (sometimes more frequent in HIV infected patients) 14 days or Neurosyphilis:
Positive lumbar puncture: Bacterial meningitis: see Chapter 7 In endemic areas: check for Tuberculous meningitis: see the MSF handbook Tuberculosis. malaria (if febrile): thick Cryptococcal meningitis: and thin films. amphotericin B IV: 0.7-1 mg/kg/d + flucytosine PO: 100 mg/kg/d for 2 weeks then fluconazole PO: 400-800 mg/d for 8 weeks Lumbar puncture (LP) if or amphotericin B IV: 0.7-1 mg/kg/d + fluconazole PO: 800 mg/d for 2 weeks not contra-indicated. then fluconazole PO alone: 400-800 mg/d for 8 weeks or, as a third option, fluconazole PO: 1200 mg/d for 2 weeks then 800 mg/d Elements favouring for 8 weeks neurosyphilis: During the induction phase: fluconazole is given by IV route (same doses) if the VDRL positive in blood patient cannot take oral treatment; liposomal amphotericin B (3 to 4 mg/kg/d, and/or CSF 2 weeks) may be used instead of conventional amphotericin B. cells in the CSF A secondary prophylaxis is recommended. high protein in the CSF Note: intracranial pressure (ICP) is often raised in cryptococcal meningitis. To lower ICP, repeated punctures to drain CSF may be necessary at the beginning of treatment.
benzylpenicilin IV: 12 to 24 MIU/day in 6 injections at 4 hour intervals for benzylpenicillin procaine IM: 2.4 g once daily + probenecid PO: 2 g/day in 4 divided doses for 10 to 14 days
Headache of no known origin: symptomatic treatment starting with a step 1 analgesic (see Pain, chapter 1).
Symptoms
Good history taking as only patients with acute episodes benefit from specific aetiological treatment (seizures, meningeal syndrome, focal signs). Positive thick and thin films: see Malaria, Chapter 6.
Diagnosis
Treatment
Aetiologies: Bacterial meningitis Tuberculous meningitis Cryptococcal meningitis Cerebral toxoplasmosis CMV meningo-encephalitis Cerebral malaria
If LP is not possible: Treat for bacterial meningitis if patient febrile and/or meningeal syndrome (see Chapter 7). Treat for toxoplasmosis if focal signs present: pyrimethamine PO: 2 mg/kg/day in 2 divided doses for 2 days In endemic areas, check for then 1 mg/kg/day + sulfadiazine PO: 80 mg/kg/d in 2 divided doses malaria (if febrile): thick + folinic acid PO: 10 mg once daily for 8 weeks and thin films. or, failing that, cotrimoxazole PO at high doses: 100 mg SMX + 20 mg TMP/kg/day in 2 divided doses for 4 weeks Lumbar puncture (LP) if A secondary prophylaxis is recommended. not contra-indicated. If the LP is positive: Bacterial meningitis: see Chapter 7 Tuberculous meningitis: see the MSF handbook Tuberculosis. Cryptococcal meningitis: amphotericin B IV: 0.7-1 mg/kg/d + flucytosine PO: 100 mg/kg/d for 2 weeks then fluconazole PO: 6-12 mg/kg/d (max. 800 mg/d) for 8 weeks or amphotericin B IV: 0.7-1 mg/kg/d + fluconazole PO: 12 mg/kg/d (max. 800 mg/d) for 2 weeks then fluconazole PO alone: 6-12 mg/kg/d for 8 weeks or, as a third option, fluconazole PO: 12 mg/kg/d (max. 1200 mg/d) for 2 weeks then 12 mg/kg/d (max. 800 mg/d) for 8 weeks During the induction phase: fluconazole is given by IV route (same doses) if the child cannot take oral treatment; conventional amphotericin B may be replaced by liposomal amphotericin B (3 to 4 mg/kg/d, 2 weeks). A secondary prophylaxis is recommended.
8. Viral diseases
219
220
Symptoms
1. History and clinical examination: look for a ENT or urinary infection, TB, skin infection, enlarged lymph nodes etc. 2. In endemic areas, check for malaria: thick and thin films. 4. Chest x-ray, CBC, blood cultures, urinalysis, stool culture, serology, lumbar puncture (LP). If the patient is under treatment, think of a fever caused by secondary effects of medication. 3. Suspected TB: look for AFB. Suspected meningitis: treat according to the results of the LP. If LP is not available, treat for bacterial meningitis, see Chapter 7. Identified or suspected focus of infection: ENT: see Chapter 2; urinary: see Chapter 9 etc. Tuberculosis: see the MSF handbook Tuberculosis.
Diagnosis
Treatment
Temperature higher than 38C, chronic (lasting more than 5 days) or recurrent (multiple episodes in a period of more than 5 days)
Positive thick and thin films: see Malaria, Chapter 6. If testing is not available: in endemic zones, give systematic malaria treatment.
Aetiologies: Infections Common childhood diseases Severe bacterial infections (TB, pneumonia, typhoid fever, septicaemia, meningitis, endocarditis etc.) Occult bacterial infections (sinusitis, otitis, urinary tract infections) Opportunistic infections (TB, mycosis, toxoplasmosis) Malaria
HIV infection
CHAPTER 9
Genito-urinary diseases
Uro-nephrologic diseases Urolithiasis Acute cystitis Acute pyelonephritis Acute prostatitis Genital infections (GI) Genital ulcers Veneral warts Metrorrhagia 223 224 226 228 229 231 233 236 239 240 243 244 246
Urethral discharge
9. Genito-urinary diseases
Urolithiasis
Partial or complete obstruction of the urinary tract by one or more calculi.
Clinical features
Acute, sometimes intense, flank or pelvic pain (renal colic). Urinalysis: haematuria, leucocyturia may be present.
Secondary infections may develop: cystitis (see page 224) or pyelonephritis (see page 226).
Treatment
In patients with infection: antibiotic treatment as for pyelonephritis (see page 226). The effectiveness will depend on the passage of the calculus.
Analgesics: For moderate pain: diclofenac PO: 150 mg/day in 3 divided doses for 3 days + hyoscine butylbromide PO: 30 to 60 mg/day in 3 divided doses for 3 days For renal colic: diclofenac IM: 75 mg/injection, 1 or 2 times/day for a maximum of 2 days then change to oral treatment + hyoscine butylbromide IM: 10 to 20 mg/injection to be repeated every 8 hours according to the clinical evolution
223
Acute cystitis
Acute cystitis
Cystitis is an infection of the bladder and urethra that affects mainly women and girls from 2 years of age. Escherichia coli is the causative pathogen in 70 to 95% of cases. Other pathogens include Proteus mirabilis, enterococcus, Klebsiella spp and in young women, S. saprophyticus.
Clinical features
Burning pain on urination and pollakiuria (passing of small quantities of urine more frequently than normal); in children: crying when passing urine; involuntary loss of urine. AND No fever (or mild fever), no flank pain; no systemic signs and symptoms in children It is essential to rule out pyelonephritis (see page 226). The symptom 'burning pain on urination' alone is insufficient to make the diagnosis. In the event of abnormal vaginal discharge, see page 233.
Laboratory
Urine dipstick test: Perform dipstick analysis for nitrites (which indicate the presence of enterobacteria) and leukocytes (which indicate an inflammation) in the urine. If dipstick analysis is negative for both nitrites and leukocytes, a urinary infection is excluded. If dipstick analysis is positive for nitrites and/or leukocytes, a urinary infection is likely. Microscopy/culture: when a dipstick analysis is positive, it is recommended to carry out urine microscopy/culture in order to confirm the infection and identify the causative pathogen, particularly in children and pregnant women. When urine microscopy is not feasible, an empirical antibiotic treatment should be administered to patients with typical signs of cystitis and positive dipstick urinalysis (leucocytes and/or nitrites). Note: aside of these results, in areas where urinary schistosomiasis is endemic, consider schistosomiasis in patients with macroscopic haematuria or microscopic haematuria detected by dipstick test, especially in children from 5 to 15 years, even if the patient may suffer from concomitant bacterial cystitis.
224
9. Genito-urinary diseases
Treatment
Cystitis in girls 2 years
cefixime PO:
or amoxicillin/clavulanic acid PO (dose expressed in amoxicillin) 25 mg/kg/day in 2 divided doses (with formulation 8:1 or 7:1 or 4:1) Note: the dose of clavulanic acid should not exceed 12.5 mg/kg/day (or 375 mg/day). Cystitis in non pregnant women If dipstick analysis is positive for both nitrites and leukocytes: fosfomycin-trometamine PO: 3 g as a single dose or ciprofloxacin PO: 500 mg/day in 2 divided doses for 3 days or nitrofurantoin PO (except in patients with G6PD deficiency): 300 mg/day in 3 divided doses for 5 days
If dipstick analysis is negative for nitrites but positive for leukocytes, the infection may be due to S. saprophyticus. Fosfomycin is not active against this pathogen. Use ciprofloxacin or nitrofurantoin, as above. Whatever the antibiotic used, symptoms may persist for 2 to 3 days despite adequate treatment. In the event of treatment failure (or recurrent cystitis i.e. > 3-4 episodes/year), ciprofloxacin PO: 1 g/day in 2 divided doses for 5 days
For patients with recurrent cystitis, consider bladder stones, urinary schistosomiasis, urinary tuberculosis or gonorrhoea (examine the partner). Cystitis in pregnant or lactating women
fosfomycine-tromethamine PO as above or cefixime PO: 400 mg/day in 2 divided doses for 5 days or nitrofurantoin PO (except in the last month of pregnancy, the first month of breastfeeding and in patients with G6PD deficiency): 300 mg/day in 3 divided doses for 5 to 7 days
225
Acute pyelonephritis
Acute pyelonephritis
Pyelonephritis is an acute infection of the renal parenchyma, potentially severe, especially in pregnant women, neonates and infants. The pathogens causing pyelonephritis are the same as those causing cystitis (see page 224).
Clinical features
Neonates and infants Symptoms are not specific: fever, irritability, vomiting, poor oral intake. Palpation of the lower abdomen may show abdominal tenderness. The absence of fever does not rule out the diagnosis. On the other hand, fever with no obvious cause may be the only manifestation. Neonates may present with fever or hypothermia, altered general condition, altered conscious state, pale/grey colour, shock.
In practice, a urinary tract infection should be suspected in children with unexplained fever or septic syndrome with no obvious focus of infection. Older children and adults Signs of cystitis (burning on urination and pollakiuria, etc.) AND Fever > 38.5C and flank pain (often unilateral) or abdominal tenderness
Laboratory
Treatment
Children under one month cefotaxime IV: 150 mg/kg/day in 3 injections for 10 days or ampicillin IV: 200 mg/kg/day in 3 injections for 10 days + gentamicin IM or IV: 5 mg/kg once daily for 5 days
Children over one month ceftriaxone IM or IV: 50 mg/kg once daily until the child's condition improves (at least 3 days), then change to oral treatment with: amoxicillin/clavulanic acid PO (dose expressed in amoxicillin): Children < 40 kg: 45 to 50 mg/kg/day in 2 doses (if using ratio 8:1 or 7:1) or in 3 doses (if using ratio 4:1) Children 40 kg: 1500 to 2000 mg/day in 2 doses (if using ratio 8:1 or 7:1) or in 3 doses (if using ratio 4:1) Note: the dose of clavulanic acid should not exceed 12.5 mg/kg/day or 375 mg/day.
226
9. Genito-urinary diseases
Treatment of fever and pain (use paracetamol rather than NSAID, see page 26). Management of septic shock if needed.
Presence of signs of serious illness (vomiting, patient seen late in disease, sepsis) or patient is in poor general condition (e.g. malnutrition, presence of other diseases) ceftriaxone IM: 1 g/once daily for at least 3 days, then change to oral treatment with cefixime PO: 400 mg/day in 2 divided doses to complete 10 to 14 days of treatment (up to 21 days depending on clinical response) + gentamicin IM: 3 to 6 mg/kg once daily for 3 days (if sepsis) or, if not available: ampicillin IV: 8 g/day in 3 injections for at least 3 days + gentamicin IM: 3 to 6 mg/kg once daily for 3 days, then change to oral treatment with amoxicillin PO: 4 g/day in 2 divided doses to complete 10 to 14 days of treatment
Pyelonephritis with no signs of serious illness ciprofloxacin PO: 1 to 1.5 g/day in 2 or 3 divided doses for 7 days or cefixime PO: 400 mg/day in 2 divided doses for 10 days
Maintain proper hydration (1.5 litre/day in adults), especially in children (risk of dehydration); treat dehydration if present (see page 315 to 321).
227
Acute prostatitis
Acute prostatitis
Acute infection of the prostate, most commonly due to Gram negative bacteria.
Clinical features
Signs of cystitis (burning on urination and urinary frequency) with fever in men, perineal pain is common. Very painful rectal examination. Urinalysis: leucocyturia and pyuria; haematuria may be present.
Treatment
Difficult, the infection may become chronic. Increase fluid intake: 3 to 4 litres/day Fever (see page 26) and pain (see page 29) Prolonged antibiotic treatment: ciprofloxacin PO: 1 g/day in 2 divided doses for 28 days
228
9. Genito-urinary diseases
Thus, the WHO has introduced the syndromic management of GI and developed standardised case management flowcharts: based on the identification of consistent groups of signs and symptoms (syndromes), patients are treated for the pathogens/ infections2 that may cause each syndrome.
Look for a genital infection if a patient complains of: Urethral discharge Painful or difficult urination (dysuria) Abnormal vaginal discharge Vulvar itching/burning Pain with intercourse (dyspareunia) Painful or difficult urination (dysuria) Urethral discharge, page 231 Abnormal vaginal discharge, page 233 Genital ulcers, page 236 See
Genital blisters or sores Burning sensation in the vulva or perineum Skin growths in the genital (or anal) area Lower abdominal pain (in women)
Lower abdominal pain, page 239 Upper genital tract infections, page 240
The patient can be effectively treated without laboratory testing. Some tests may help in diagnosing vaginal and urethral discharge, but they should never delay treatment (results should be available within one hour). Single dose regimens are preferred when indicated.
The patient should be treated at his/her first encounter with the health care provider (no patient should be sent home without treatment, e.g. while waiting for laboratory results).
In the case of urethral discharge, abnormal vaginal discharge (except candidiasis), genital ulcers (except herpes) and sexually transmitted upper genital tract infection, the sexual partner should receive a treatment. In the case of candidiasis, genital herpes and venereal warts, the partner is treated only if symptomatic.
1 Genital infections may be sexually transmitted (e.g. gonorrhoea, chlamydia) or not (e.g. most cases of 2 Keep in mind that in Schistosoma haematobium endemic areas, genital symptoms may also be due to, or
Patients with sexually transmitted infections should receive information on their disease(s) and treatment and be counselled on risk reduction and HIV testing. Condoms should be provided for the duration of treatment.
candidiasis).
229
Taking into consideration the physical, psychological, legal and social consequences of sexual violence, medical care is not limited to the diagnosis and treatment of genital lesions or infections.
Care includes listening to the victims story, a complete physical examination, laboratory tests if available, and completion of a medical certificate (see Practical advice for writing medical certificates in the event of sexual violence, page 312). During the consultation, prophylactic or curative treatments must be proposed to the patient. Prophylactic treatment: priority is given to the risk of HIV transmission (earliest possible antiviral therapy for patients seen within 48-72 hours after exposure, see HIV infection and AIDS, page 207) and to the risk of pregnancy resulting from rape (administer emergency contraception as soon as possible, ideally within 72 hours of exposure: levonorgestrel PO: one 1500 g tablet or two 750 g tablets as a single dose)3; prevention of sexually transmitted infections includes a single dose treatment with azithromycin 1 g + cefixime 400 mg. If necessary, treatment of trichomoniasis may follow; tetanus prophylaxis and/or vaccination (see Tetanus, page 170) if there are any wounds; vaccination against hepatitis B (see Viral hepatitis, accelerated vaccination schedule, page 200). Curative treatment: of wounds, of any related pathologies/infections if the assault is not recent. Mental health care is necessary irrespective of any delay between the event and the patient arriving for a consultation. Care is based on immediate attention (one-on-one reception and listening) and if necessary, follow-up care with a view to detecting and treating any psychological and/or psychiatric sequelae (anxiety, depression, posttraumatic stress disorder, etc.). See Chapter 11.
3 Genital infections may be sexually transmitted (e.g. gonorrhoea, chlamydia) or not (e.g. most cases of
candidiasis).
230
9. Genito-urinary diseases
Urethral discharge
Urethral discharge is seen almost exclusively in men. The principal causative organisms are Neisseria gonorrhoeae (gonorrhoea) and Chlamydia trachomatis (chlamydia). The presence of abnormal discharge should be confirmed by performing a clinical examination1. In males, the urethra should be milked gently if no discharge is visible. Furthermore, specifically check for urethral discharge in patients complaining of painful or difficult urination (dysuria).
Case management
The patient complains of urethral discharge or dysuria Take history and examine Urethral discharge is present?
YES NO
NO
Laboratory
C. trachomatis cannot easily be identified in a field laboratory. In the absence of validated rapid diagnostic tests, the treatment is empiric. In men, a methylene blue or Gram stained smear from a urethral swab may be used to detect gonococci (Gram negative intracellular diplococci).
1 In areas where lymphatic filariasis is endemic, be careful not to confuse purulent urethral discharge with milky or
231
Urethral discharge
In men: If microscopy of a urethral smear has been performed: in the absence of gonococci, treat for chlamydia alone; in the presence of gonococci, treat for chlamydia AND gonorrhoea. When no laboratory is available, treat for chlamydia AND gonorrhoea. In women: Treat for chlamydia AND gonorrhoea.
or
1 g as a single dose
PLUS
cefixime PO:
ceftriaxone IM:
or
spectinomycin IM:
or
or
azithromycin PO:
erythromycin PO:
If urethral discharge persists or reappears after 7 days: Verify that the patient has received an effective treatment (i.e. one of the combinations above). Gonococcal resistance is a possibility if another treatment (e.g. cotrimoxazole or kanamycin) has been administered: re-treat for gonorrhoea as above (chlamydia is rarely resistant). If an effective antibiotic therapy has been given, consider trichomoniasis (tinidazole or metronidazole PO, 2 g as a single dose); also consider re-infection.
1 g as a single dose
cefixime PO:
ceftriaxone IM:
The sexual partner receives the same treatment as the patient, whether or not symptoms are present.
232
9. Genito-urinary diseases
Abnormal vaginal discharge may be a sign of infection of the vagina (vaginitis) and/or the cervix (cervicitis) or upper genital tract infection. The presence of abnormal discharge must be confirmed by performing a clinical examination: inspection of the vulva, speculum exam (checking for cervical/vaginal inflammation or discharge). Abdominal and bimanual pelvic examinations should be performed routinely in all women presenting with vaginal discharge to rule out upper genital tract infection (lower abdominal pain and cervical motion tenderness). The principal causative organisms are: In vaginitis: Gardnerella vaginalis and other bacteria (bacterial vaginosis), Trichomonas vaginalis (trichomoniasis) and Candida albicans (candidiasis). In upper genital tract infections: see page 240.
Case management
Laboratory
Identification of N. gonorrhoeae by Gram stained smear is not sensitive in women and is not recommended.
Tests usually available in the field can only identify causes of vaginitis, and thus are of limited usefulness. Microscopic examination of a fresh wet smear may show mobile T. vaginalis, yeast cells and hyphae in candidiasis, and clue cells in bacterial vaginosis.
233
Case management
Patient complains of vaginal discharge or vulvar itching/burning, etc. Take history, examine and assess risk factors Abnormal discharge is present?
YES NO
Look for another genital disorder. If present, treat appropriately. If not, reassure the patient. See Lower abdominal pain, page 239
YES
YES
YES
Cervicitis may be difficult to diagnose. When in doubt, administer treatment for cervicitis to women with abnormal vaginal discharge and any of the following risk factors: Urethral discharge in the partner Context of sexual violence or prostitution New partner or more than one partner in the preceding 3 months
234
9. Genito-urinary diseases
1 g as a single dose
PLUS
cefixime PO:
ceftriaxone IM:
or
azithromycin PO:
erythromycin PO:
1 g as a single dose
or
or
ceftriaxone IM:
dose
Vulvovaginal candidiasis
If the patient has extensive vulvar involvement, miconazole 2% cream (2 applications to the vulva daily for 7 days) may be used in combination with the intravaginal treatment above. Miconazole cream may complement, but does not replace, treatment with clotrimazole.
clotrimazole (500 mg vaginal tablet): 1 tablet as a single dose, inserted deep into the vagina at bedtime or, if not available, clotrimazole (100 mg vaginal tablet): one tablet inserted deep into the vagina at bedtime for 6 days or nystatin (100,000 IU vaginal tablet): one tablet inserted deep into the vagina at bedtime for 14 days
When the patient is treated for vaginitis or cervicitis, the sexual partner receives the same treatment as the patient, whether or not symptoms are present. In the case of vulvovaginal candidiasis, the partner is treated only if symptomatic (itching and redness of the glans/prepuce): miconazole 2%, 2 applications daily for 7 days.
235
Genital ulcers
Genital ulcers
Genital ulcers, defined as single or multiple vesicular, ulcerative or erosive lesions of the genital tract, with or without inguinal lymphadenopathy, should lead to consideration of sexually transmitted infection. The principal causative organisms are Treponema pallidum (syphilis), Haemophilus ducreyi (chancroid) and Herpes simplex (genital herpes). Chlamydia trachomatis (lymphogranuloma venereum) and Calymmatobacterium granulomatis (donovanosis)1 are less frequent.
Case management
Patient complains of genital sore or ulcer Take history and examine Sore/ulcer/vesicle is present?
YES NO
Look for another genital disorder. If present, treat appropriately. If not, reassure the patient.
Small painful vesicles, sometimes in clusters, or small ulcers with history of recurrent vesicles?
NO
YES
Treat for syphilis AND chancroid In endemic areas, also treat for lymphogranuloma venereum AND/OR donovanosis Refer if necessary
Laboratory
Laboratory testing available in the field is of little value: e.g., in syphilis, a negative RPR or VDRL result does not exclude primary syphilis in early stage, and a positive test may reflect previous infection in a successfully treated patient.
1 Lymphogranuloma venereum is endemic in East and West Africa, India, Southeast Asia, South America and the
Caribbean. Donovanosis is endemic in South Africa, Papua New Guinea, India, Brazil and the Caribbean.
236
9. Genito-urinary diseases
Antiviral treatment: aciclovir PO In patients with a first episode, treatment may reduce the duration of symptom when given within 5 days after the onset of symptoms: 1200 mg/day in 3 divided doses for 7 days In patients with recurrence, give the same dose for 5 days, but treatment is only effective if initiated during the prodromal phase or within 24 hours after the onset of symptoms. In patients with frequent recurrences (more than 6 episodes/year), see HIV infection and AIDS, page 212. Syphilis Treatment of pain: paracetamol PO
benzathine benzylpenicillin IM: 2.4 MUI/injection (half the dose in each buttock). Administer a single dose for early syphilis (less than 2 years); one injection per week for 3 weeks for late syphilis (more than 2 years) or if the duration of infection is unknown. or, for penicillin-allergic patients: doxycycline PO: 200 mg/day in 2 divided doses for 14 days2 or erythromycin PO: 2 g/day in 2 or 4 divided doses for 14 days
Chancroid or or
ciprofloxacin PO:
Note: treat simultaneously for syphilis AND chancroid as both are frequent, and cannot be correctly distinguished on clinical grounds. Lymphogranuloma venereum
doxycyclin PO:
Fluctuant lymph nodes may be aspirated through healthy skin as required. Do not incise and drain lymph nodes.
or
1 g as a single dose
erythromycin PO:
Fluctuant lymph nodes may be aspirated through healthy skin as required. Do not incise and drain lymph nodes.
2 Doxycycline is contra-indicated in pregnant women and breast-feeding women. 3 Ciprofloxacin should be avoided in pregnant women.
or
erythromycin PO:
237
Genital ulcers
Donovanosis
Treatment is given for a minimum of 14 days, longer if necessary, until the complete disappearance of the lesions (otherwise risk of recurrence): azithromycin PO: 1 g the first day then, 500 mg once daily or doxycyline PO: 200 mg/day in 2 divided doses4 or erythromycin PO: 2 g/day in 2 or 4 divided doses In HIV infected patients, add gentamicin IM: 3 to 6 mg/kg/day in 1 or 2 injections.
The sexual partner receives the same treatment as the patient, whether or not symptoms are present, except in the case of genital herpes (the partner is treated only if symptomatic).
238
9. Genito-urinary diseases
Case management
Patient complains of lower abdominal pain Following delivery or abortion? Take history and examine Any of the following present? Amenorrhoea Abnormal vaginal bleeding Abdominal guarding or rebound tenderness
YES NO
YES
NO
NO
See Sexually transmitted UGTI, page 240. Review in 3 days. Patient has improved? Continue treatment until completed
YES NO
* Look for another cause (in particular, gastrointestinal or urinary pathology). ** Look for a pregnancy related pathology (threatened abortion, extra-uterine pregnancy) or a complication (peritonitis, pelvic abscess).
239
Clinical features
Sexually transmitted infections Diagnosis may be difficult, as clinical presentation is variable. Suggestive symptoms are: abdominal pain, abnormal vaginal discharge, fever, dyspareunia, menometrorrhagia, dysuria. Infection is probable when one or more of the above symptoms are associated with one or more of the following signs: cervical motion tenderness, adnexal tenderness, tender abdominal mass. Most cases present with a typical clinical picture, developing within 2 to 10 days after delivery (caesarean section or vaginal delivery) or abortion (spontaneous or induced): Fever, generally high Abdominal or pelvic pain Malodorous or purulent lochia Enlarged, soft and/or tender uterus Check for retained placenta. In the early stages, fever may be absent or moderate and abdominal pain may be mild. Infections after childbirth or abortion
Treatment
All other patients may be treated on an ambulatory basis. They should be reassessed routinely on the third day of treatment to evaluate clinical improvement (decrease in pain, absence of fever). If it is difficult to organise routine follow-up, advise patients to return to clinic if there is no improvement after 48 hours of treatment, or sooner if their condition is worsening.
240
Criteria for hospitalisation include: Clinical suspicion of severe or complicated infection (e.g. peritonitis, abscess, septicaemia) Diagnostic uncertainty (e.g. suspicion of extra-uterine pregnancy, appendicitis) Significant obstacles to ambulatory oral treatment No improvement after 48 hours, or deterioration within 48 hours, of outpatient treatment
9. Genito-urinary diseases
If an IUD is in place, it should be removed (offer another method of contraception). Analgesic treatment according to pain intensity. Treatment of the partner: single dose treatment for both gonorrhoea AND chlamydia (as for Urethral discharge, page 231), whether or not symptoms are present. Infections after childbirth or abortion
Antibiotic therapy combines 3 antibiotics to cover the most frequent causative organisms: gonococci, chlamydiae, and anaerobes. Ambulatory treatment: cefixime PO: 400 mg as a single dose or ceftriaxone IM: 250 mg as a single dose + doxycycline PO: 200 mg/day in 2 divided doses for 14 days1 + metronidazole PO: 1 g/day in 2 divided doses for 14 days Treatment in hospital: ceftriaxone IM: 250 mg/day once daily + doxycycline PO: 200 mg/day in 2 divided doses for 14 days1 + metronidazole PO or IV: 1 g/day in 2 divided doses or infusions for 14 days Continue triple therapy for 24 to 48 hours after signs and symptoms have improved (resolution of fever, decrease in pain), then continue doxycycline (or erythromycin) + metronidazole to complete 14 days of treatment.
Antibiotic therapy: treatment must cover the most frequent causative organisms: anaerobes, Gram negatives and streptococci. Ambulatory treatment (early stages only): amoxicillin/clavulanic acid (co-amoxiclav) PO for 7 days The dose is expressed in amoxicillin. Depending on the formulation of coamoxiclav available: Ratio 8:1: 3000 mg/day = 2 tablets of 500/62.5 mg 3 times per day Ratio 7:1: 2625 mg/day = 1 tablet of 875/125 mg 3 times per day Note: the dose of clavulanic acid should not exceed 375 mg/day. or amoxicillin PO: 3 g/day in 3 divided doses + metronidazole PO: 1.5 g/day in 3 divided doses for 7 days Treatment in hospital: amoxicillin/clavulanic acid (co-amoxiclav) IV (dose expressed in amoxicillin): 3 g/day in 3 injections + gentamicin IM: 5 mg/kg once daily or ampicillin IV: 6 g/day in 3 injections + metronidazole IV: 1.5 g/day in 3 infusions + gentamicin IM: 5 mg/kg once daily Once the patients condition has improved and oral treatment can be tolerated, coamoxiclav or amoxicillin + metronidazole may be given PO (as for ambulatory treatment). Stop antibiotic therapy 48 hours after resolution of fever and improvement in pain.
1 In pregnant/breastfeeding women: erythromycin PO: 2 g/day in 2 to 4 divided doses for 14 days
Single dose azithromycin is not effective against chlamydia in the treatment of sexually transmitted UGTI. 241
In case of placental retention: perform digital curettage or manual vacuum extraction (refer to the MSF handbook Obstetrics) 24 hours after initiation of antibiotic therapy. Analgesic treatment according to pain intensity. If the patients condition deteriorates or if fever persists after 48-72 hours of treatment, consider the possibility of complication requiring additional treatment (e.g. pelvic abscess drainage), otherwise change the antibiotic to ceftriaxone + doxycycline + metronidazole as in hospital-based treatment of sexually transmitted UGTI.
In penicillin-allergic patients, use clindamycin (2700 mg/day in 3 divided doses or injections) + gentamicin (5 mg/kg once daily).
242
9. Genito-urinary diseases
Veneral warts
Venereal warts are benign tumours of the skin or mucous membranes due to certain papilloma viruses (HPV).
Clinical features
Venereal warts are soft, raised, painless growths, sometimes clustered (cauliflowerlike appearance) or macules (flat warts), which are more difficult to discern. Warts can be external (vulva, penis, scrotum, perineum, anus) and/or internal (vagina, cervix, urethra, rectum; oral cavity in HIV infected patients). In women, the presence of external warts is an indication for a speculum examination to exclude vaginal or cervical warts. Speculum exam may reveal a friable, fungating tumour on the cervix, suggestive of cancer associated with papilloma virus1.
Treatment
External warts < 3 cm and vaginal warts podophyllotoxin 0.5%2 solution may be self-applied by the patient, but in the event of vaginal warts, the treatment must be applied by medical staff. Explain the procedure to the patient: apply the solution to the warts using an applicator or cotton bud, sparing the surrounding healthy skin, allow to air dry. On vaginal warts, the solution should be allowed to dry before the speculum is withdrawn. Apply the solution twice daily, 3 consecutive days per week, for up to 4 weeks. Podophyllum preparations are contra-indicated in pregnant3 or breastfeeding women. They should not be applied on cervical, intra-urethral, rectal, oral or extensive warts. Improper use may result in painful ulceration. External warts > 3 cm; cervical, intra-urethral, rectal and oral warts; warts in pregnant or breastfeeding women Surgical excision or cryotherapy or electrocoagulation.
Choice of treatment depends on the size and location of the warts. Treatment may be less effective, and relapses more frequent, in HIV infected patients.
1 Certain types of HPV may cause cancer. Presence of genital warts in women is an indication to screen for
pre-cancerous lesions of the cervix, if feasible in the context (visual inspection with acetic acid, or cervical smear, or other available techniques), and to treat any lesions identified (cryotherapy, conisation, etc., according to diagnosis). 2 Podophyllum 10%, 15% or 25% resin is another preparation which is much more caustic, and should be applied only by medical staff. Protect the surrounding skin (vaseline or zinc oxide ointment) before applying the resin. Wash off with soap and water after 1 to 4 hours. Apply once weekly for 4 weeks. 3 Treatment of warts is not an emergency and may be deferred if alternatives to podophyllum preparations are not available. Genital warts are not an indication for caesarean section: it is uncommon for warts to interfere with delivery, and the risk of mother-to-child transmission is very low. 243
244
Clinical features
In women: vaginal discharge, cervicitis (mucopurulent cervical discharge), dysuria (50% of infections are asymptomatic); UGTI (salpingitis, endometritis). In men: purulent urethral discharge and sometimes dysuria (5 to 50% of infections are asymptomatic).
In women: vaginal discharge, cervicitis, and rarely dysuria (> 50% of infections are asymptomatic); UGTI (salpingitis, endometritis). In men: mild urethral discharge and/or dysuria but up to 90% of infections are asymptomatic. dose
Diagnosis is made in the presence of 3 of the following 4 signs: Homogenous grey-white adherent vaginal discharge pH of vaginal fluid > 4.5 Vaginal fluid has an amine (fishy) odour, especially when mixed with 10% KOH Presence of clue cells in wet mount or Gram stain of vaginal fluid
In women: yellow-green vaginal discharge, sometimes Wet mount of fresh vaginal fluid foul smelling, vulvar irritation (10 to 50% of infections shows motile trichomonas (low are asymptomatic). sensitivity). In men: most infections are asymptomatic. Can pH of urethral/vaginal fluid > 4.5 produce balanitis, urethritis with mild discharge and sometimes dysuria. dose
Mainly seen in women: pruritus and vulvovaginitis, Saline of KOH wet mount of fresh frequently creamy-white vaginal discharge, somevaginal fluid shows budding yeast times dysuria. cells and pseudohyphae. In men: balanitis/balanoposthitis (inflammation of pH of vaginal fluid: normal the glans/prepuce, erythema, pruritus, white pustules) and rarely urethritis
a single dose or clotrimazole 100 mg: one vaginal tablet/day for 6 days or nystatin 100,000 IU: one vaginal tablet/day for 14 days In men: miconazole 2% cream: 2 applications daily for 7 days
In women:
Clinical features
Many asymptomatic carriers. Multiple vesicles on Diagnosis by culture, serology and genitals leading to painful ulcerations. PCR done exclusively at a reference In women, affects vulva, vagina and cervix; in males, laboratory. penis and sometimes urethra. In primary episodes, fever (30%) and lymphadenopathy (50%). Recurrences in 1/3 of infections with shorter and milder symptoms. RPR/VDRL lack sensitivity and specificity, but may be useful for following treatment effectiveness (decrease in titer) or confirming reinfection (rise in titer). Treponemic tests (TPHA, FTA, rapid tests such as SD Bioline) are more sensitive and specific.
Analgesics, local disinfection. If available, aciclovir PO: Primary episode: 1200 mg/day for 7 days, given within 5 days after onset of lesions. Recurrent infections: same dose for 5 days, given within 24 hours after onset of lesions. 2.4 MIU/injection, single dose (syphylis < 2 years) or one injection/week for 3 weeks (syphilis > 2 years or unknow duration) For penicillin-allergic patients: doxycycline PO1: 200 mg/day for 14 days or erythromycin PO: 2 g/day for 14 days Treat also for chancroid.
azithromycin PO: 1 g as a single dose or ceftriaxone IM: 250 mg as a single dose or ciprofloxacin PO2: 1 g/day for 3 days or erythromycin PO: 2 g/day for 7 days Treat also for syphillis.
Painful single (or multiple) genital ulcer (soft chancre, bleeds easily when touched). Painful and voluminous inguinal lymphadenitis in 50%. Fistulae develop in 25% of cases.
Soft, raised, painless growths, sometimes clustered (acuminate condyloma) or macules (flat warts). Warts can be external (vulva, penis, scrotum, perineum, anus) and/or internal (vagina, cervix, urethra, rectum; oral cavity in HIV infected patients).
1 Doxycycline is contra-indicated in pregnant women. It should not be administered to breast-feeding women if the treatment exceeds 7 days (use
The diagnosis is based on clinical External warts < 3 cm and vaginal warts: features. podophyllotoxin 0.5% It feasible in the context, the presence of External warts > 3 cm; cervical, intragenital warts in women in an indication urethral, rectal and oral warts; warts in to screen for pre-cancerous lesions of the pregnant or breastfeeding women: surgical cervix (visual inspection with acetic excision or cryotherapy or electrocoagulation. acid, or cervical smear, or other available techniques).
9. Genito-urinary diseases
erythromycin).
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Metrorrhagia
Metrorrhagia
Genital bleeding unrelated to the menstrual period. In women of childbearing age, always assess if the bleeding is related to a pregnancy.
In all events
Rapidly assess the severity of bleeding. In the event of heavy haemorrhage or shock or if a surgical intervention (laparotomy, caesarean delivery) is required: Start an IV infusion of Ringer lactate; monitor vital signs (pulse, BP); Prepare for a possible blood transfusion (determine patient's group, identify potential donors); If a transfusion is performed, only use blood that has been screened at least for HIV, hepatitis B, and hepatitis C. In the event of referral to a surgical facility, difficult transport conditions might aggravate the haemorrhage: the patient should be infused and accompanied by family members who are potential blood donors. Ultrasound is not imperative but it facilitates certain diagnoses (e.g. ectopic pregnancy, placenta praevia). Prevent or treat anaemia. Clinical examination: speculum examination: determine the origin of the bleeding [vagina, cervix, uterine cavity]; appearance of the cervix; estimation of blood loss; bimanual pelvic examination: look for uterine motion tenderness, increased volume or abnormalities of the uterus. Friable, hard, ulcerated, hypertrophic mass on the cervix: possible cervical cancer; surgical treatment is required. While waiting for surgery, tranexamic acid PO (3 g/day in 3 divided doses for 3 to 5 days) may be used to reduce bleeding. Inflammation of the cervix, light or moderate bleeding, purulent cervical discharge, pelvic pain: consider cervicitis (see Abnormal vaginal discharge, page 233) or salpingitis (see Upper genital tract infections, page 240). Enlarged, misshapen uterus: uterine fibroids; surgical treatment if large fibroids cause significant bleeding. While waiting for surgery or if surgery is not indicated, treat as a functional uterine bleeding. Normal uterus and cervix: possible functional uterine bleeding: tranexamic acid PO as above. In situations of repeated bleeding, it can be combined with an NSAID (ibuprofen PO: 1200 to 2400 mg/day maximum, in 3 divided doses for 3 to 5 days) and/or a long-term treatment with oral estroprogestogens or injectable progestogens. Note: rule out other causes of vaginal bleeding before diagnosing functional uterine bleeding. Consider for example poorly tolerated contraceptive, endometrial cancer in postmenopausal women, genitourinary schistosomiasis in endemic areas (page 151).
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9. Genito-urinary diseases
The two diagnoses to firstly consider are ectopic pregnancy and abortion.
Ectopic pregnancy
Pregnancy that develops outside the uterus, very often in a fallopian tube. Ectopic pregnancy should be suspected in any woman of reproductive age with pelvic pain and/or metrorrhagia. There are many possible clinical presentations and these can mislead diagnosis towards appendicitis, intestinal obstruction, salpingitis or abortion. The major risk of ectopic pregnancy is rupture, leading to intra abdominal haemorrhage. Clinical features and diagnosis Amenorrhoea (may be absent) or menstrual irregularity. Dark slight bleeding or light to heavy bright red bleeding; or haemorrhagic shock with light bleeding not corresponding to the severity of shock (intra-abdominal haemorrhage). Pelvic pain; sometimes distended abdomen, rebound tenderness. On pelvic examination: tender adnexal mass; exquisite pain in the Pouch of Douglas (haemoperitoneum); closed cervix. The diagnosis of pregnancy is confirmed by a positive rapid pregnancy test (urinary test) but a negative urinary test does not rule out an ectopic pregnancy. If ultrasound is available, the presence of an intra-uterine pregnancy eliminates the diagnosis of an ectopic pregnancy. If ultrasound shows an empty uterus together with intra peritoneal effusion, an ectopic pregnancy is likely, especially if the pregnancy test is positive. Management If in doubt (negative pregnancy test, no sign of rupture and stable haemodynamic conditions), hospitalise the patient for surveillance, if possible in a surgical facility. Otherwise, refer immediately for emergency laparotomy.
Threatened abortion
Clinical features Management In a context of amenorrhoea: slight, bright red bleeding; pelvic pain; closed cervix. Look for foreign bodies or vaginal wound consistent with induced abortion; remove foreign bodies, clean the wound; update tetanus immunization (page 170). Treat pain: paracetamol or antispasmodics PO. Place the patient on rest.
Abortion
Clinical features Slight or significant bright red bleeding; expulsion of the embryo, membranes or products; uterine contractions; open cervix.
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Metrorrhagia
Management
Look for foreign bodies or vaginal wound consistent with induced abortion; remove foreign bodies, clean the wound; update tetanus immunization (page 170). Treat pain: paracetamol or antispasmodics.
Depending on the stage of pregnancy: Before 10 weeks of pregnancy: abortion is likely to be complete. Monitor, only intervene in the event of heavy bleeding (aspiration). Between 10 and 12 weeks of pregnancy: uterine evacuation is often necessary. Manual vacuum aspiration is the method of choice (easier to perform, less traumatic and less painful than curettage). Administration of misoprostol (600 g PO as a single dose) can be used to avoid instrumental evacuation but carries a risk of failure. It is essential to check if the uterus is empty a few days after administration. If the treatment has failed, instrumental evacuation is unavoidable. After 12 weeks of pregnancy: labour should be allowed to progress, do not rupture the membranes. The placenta is usually evacuated with the foetus. If evacuation is incomplete or in the event of haemorrhage, perform manual removal immediately after the expulsion, before the uterus retracts or the cervix closes. If manual removal is delayed, curettage must be performed which carries a high risk of uterine perforation. In the event of post-abortion infection (pelvic pain, uterine tenderness, foul-smelling vaginal discharge): antibiotic treatment, see Upper genital tract infections, page 241.
Three conditions placenta praevia, abruptio placentae, and uterine rupturecan quickly become life-threatening to both mother and child. These conditions must be referred to surgical facilities. When no cause for the bleeding is found, consider the possibility of premature labour.
Placenta praevia
Placenta that covers either entirely or partially the internal os of the cervix. Placenta praevia may give rise to bleeding during the third trimester and carries a high risk of haemorrhage during delivery. Clinical features and diagnosis Sudden, painless, slight or significant bright red bleeding. The vaginal exam must be done with extreme care to avoid triggering massive bleeding: uterus is soft; the exam may reveal displacement of the cervix and deformation of the lower uterine segment by the placenta praevia; if the cervix is dilated, the placenta can be felt in the cervix. Do not repeat the examination. If ultrasound is available, vaginal examination can be avoided. Management If labour has not yet started and bleeding is light: bed rest and monitoring. If labour has started and/or bleeding is heavy: refer to surgical facility.
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9. Genito-urinary diseases
Abruptio placenta
Haematoma that forms between the placenta and the uterine wall as a result of separation of the placenta, prior to foetal expulsion. Clinical features Dark slight bleeding, sometimes absent, or shock not always consistent with the external blood loss as bleeding is internal. Sudden, severe, continuous abdominal pain. Tightly contracted uterus; often, foetal heart sounds absent (foetal death). Often occurs in a context of pre-eclampsia. Management Refer to surgical facility.
Uterine rupture
Tear in the uterine wall, in most cases during labour, often related to inappropriate use of oxytocin. Clinical features Impending rupture: prolonged labour, agitation, alteration of the general state, poor uterine relaxation, continuous abdominal pain, more severe than the contractions. Rupture: disappearance of uterine contractions, shock; sometimes, palpation of the dead foetus expelled into the maternal abdomen. Management Refer to surgical facility for emergency laparotomy.
Premature labour
Clinical features Cervical changes (effacement and dilatation) and regular uterine contractions before 37 weeks LMP. Metrorrhagia are not always present in premature labour. If present, blood loss is usually minimal. Management Strict bed rest. Allow labour to progress in the following cases: gestation is more than 37 weeks; the cervix is more than 3-4 cm dilated; there is significant bleeding; the foetus is distressed or dead; there is amnionitis or pre-eclampsia. Otherwise, tocolysis: As first-line treatment, nifedipine PO (short-acting capsule): 10 mg by oral route, to be repeated every 15 minutes if uterine contractions persist (maximum 4 doses or 40 mg), then 20 mg every 6 hours for 48 hours.
249
Metrorrhagia
or, if not available, salbutamol IV infusion for 48 hours maximum: dilute 5 mg (10 ampoules of 0.5 mg) in 500 ml of 5% glucose or 0.9% sodium chloride to obtain a solution of 10 micrograms/ml. Start infusion at the rate of 15 to 20 micrograms/minute (30 to 40 drops/minute). If contractions persist, increase the rate by 10 to 20 drops/minute every 30 minutes until uterine contractions cease. Do not exceed 45 micrograms/minute (90 drops/minute). Continue for one hour after contractions have ceased, then reduce the rate by half every 6 hours. Monitor maternal pulse regularly, decrease the infusion rate in the event of maternal tachycardia (> 120/minute). Either tocolysis is effective and contractions cease or diminish: in both cases, do not prolong treatment over 48 hours. Bed rest until the end of pregnancy. Or tocolysis is not effective, contractions persist and labour begins: take necessary steps for a premature birth. Do not combine nifedipine and salbutamol.
Post-partum haemorrhage
Clinical features Haemorrhage, exceeding the usual 500 ml of a normal placental delivery that occurs in the first 24 hours (usually immediately) following the delivery of the child. Postpartum haemorrhage is mainly due to placental retention and uterine atonia, but may also result from uterine rupture or cervical or vaginal lacerations. Management
If systolic BP is < 90 mmHg, elevate the legs (keep or replace the patient's feet in the delivery table stirrups). Under general anaesthesia and antibiotic prophylaxis (ampicillin or cefazolin IV, 2 g as a single dose): manual removal of the placenta (if not yet delivered) and systematic manual exploration of the uterus to remove any clots/placental debris and to make sure the uterus has not ruptured. Then oxytocin: 10 IU diluted in 500 ml of Ringer lactate, at a rate of 80 drops/minute. At the same time, administer 5 to 10 IU by IV push, to be repeated if necessary until retraction of uterus, without exceeding a total dose of 60 IU. Massage of the uterus to expel any clots and aid uterine retraction. Continue monitoring (pulse, BP, blood loss). Bleeding should diminish and the uterus should remain firm. Measure haemoglobin. Insert a urinary catheter to facilitate uterine retraction. For more information on the management of pregnancy-related bleeding, refer to the MSF handbook, Obstetrics.
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CHAPTER 10
Abscesses
10
Dressings
The objective of dressing wounds is to promote healing. The procedure includes cleaning, disinfection and protection of the wound while respecting the rules of hygiene.
Not all wounds need to be covered by a dressing (e.g. a clean wound that has been sutured for several days; a small dry wound not requiring sutures).
Material
Renewable supplies sterile compresses non-sterile disposable gloves adhesive tape and/or crepe or gauze bandage sterile 0.9% sodium chloride or sterile water depending on the wound: antiseptic (polyvidone iodine scrub solution, polyvidone iodine dermal solution), paraffin compresses, analgesics
Sterile instruments one Kocher or Pean forceps one dissecting forceps one pair of surgical scissors or one scalpel to excise necrotic tissue and to cut gauze or sutures Instruments for one dressing for one patient must be wrapped together in paper or fabric (or can be placed in a metallic box) and sterilised together to limit handling and breaks in asepsis. 5 to 10 compresses may be included in this set. If there are no sterile instruments, a dressing can be done using sterile gloves.
Organisation of care
Proper organization of care helps maintain the rules of asepsis and decreases the risk of contamination of the wound or transmission of organisms from one patient to another: Assign one room for dressings. It must be cleaned and the waste removed every day. The dressing table must be disinfected after each patient. Dressings may be applied at the bedside if the patients condition requires. Use a clean, disinfected dressing trolley with: on the upper tray, sterile and/or clean material (dressing set, extra compresses, etc.) and on the lower tray, septic material (container for contaminated instruments, sharps disposal container and a container or garbage bag for waste).
10
Prepare all the necessary material in a well lit area. If necessary, arrange for an assistant to be present. Wear protective glasses if there is a risk of projection from an oozing wound.
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Dressings
Always proceed from clean to dirty: start with patients with uninfected wounds. If there are multiple dressings for one patient, start with the cleanest wound.
Technique
If the procedure may be painful, give an analgesic and wait the necessary time for the drug to take effect before starting the procedure. Explain the procedure to the patient and obtain his co-operation.
Settle the patient comfortably in an area where his privacy is respected throughout the procedure. Instruments (or sterile gloves) must be changed between patients. To prevent drug interactions, use the same antiseptic for all care of one patient.
Wash hands (ordinary soap) or disinfect them with an alcohol-based hand rub.
Put on non-sterile gloves and remove the adhesive tape, bandage and superficial compresses.
Proceed gently with the last compresses. If they stick to the wound, loosen them with 0.9% sodium chloride or sterile water before removal. Discard the dressing and the non-sterile gloves in the waste container.
Observe the soiled compresses. If there is significant discharge, a greenish colour or a foul odour, a wound infection is likely.
In the case of an open wound, loss of cutaneous tissue or ulcer, the colour is an indicator of the stage in the healing process: black area = necrosis, wet or dry infected eschar yellow or greenish area = infected tissue and presence of pus red area = granulation, usually a sign of healing (unless there is hypertrophy), however, red edges indicate inflammation or infection pink area = process of epithelisation, the final stage of healing that begins at the edges of the wound
In the case of a sutured wound, the existence of local signs of suppuration and pain requires the removal of one or more sutures to avoid the infection spreading. Local signs include: red, indurated and painful edges drainage of pus between the sutures, either spontaneously or when pressure is applied on either side of the wound lymphangitis sub-cutaneous crepitations around the wound
In any case, if local signs of infection are observed, look for general signs of infection (fever, chills, changes in the overall condition).
254
Open the dressing set or box after checking the date of sterilisation and that the wrapping is intact. Pick up one of the sterile forceps being careful not to touch anything else. Pick up the second forceps with the help of the first one. Make a swab by folding a compress in 4 using the forceps.
Clean sutured wound or clean open wound with red granulation: clean with 0.9% sodium chloride or sterile water to remove any organic residue; work from the cleanest to the dirtiest area (use a clean swab for each stroke); dab dry with a sterile compress; re-cover a sutured wound with sterile compresses or an open wound with paraffin compresses; the dressing should extend a few cm beyond the edges of the wound; keep the dressing in place with adhesive tape or a bandage.
Necrotic or infected open wounds: clean with polyvidone iodine (7.5% scrub solution, 1 part of solution + 4 parts of sterile 0.9% sodium chloride or sterile water). Rinse thoroughly then dab dry with a sterile compress; or if not available, sterile 0.9% sodium chloride or sterile water and apply an antiseptic (10% polyvidone iodine dermal solution). apply sterile vaseline and remove all necrotic tissue at each dressing change until the wound is clean. Discard any sharp materials used in an appropriate sharps container and the rest of the waste in a waste container. As quickly as possible, soak the instruments in disinfectant. Wash hands again or disinfect them with an alcohol-based hand rub. The principles remain the same if the dressing is done using instruments or sterile gloves.
Subsequent dressings
Clean, sutured wound: remove the initial dressing after 5 days if the wound remains painless and odourless, and if the dressing remains clean. The decision to re-cover or to leave the wound uncovered (if it is dry) often depends on the context and local practices. Open, dirty wound: daily cleaning and dressing change.
Infected, sutured wound: remove one or more sutures and evacuate the pus. Change the dressing at least once daily. Open granulating wound: change the dressing every 2 to 3 days, except if the granulation is hypertrophic (in this case, apply local corticosteroids).
10
255
The goal of treatment is to assure rapid healing of the wound without complications or sequelae. Several basic rules apply:
immediately suture recent, clean, simple wounds (less than 6 hours old) and delay suturing contaminated wounds and/or those more than 6 hours old;
Material
One dissecting forceps, one needle-holder, one pair of surgical scissors and one Pean or Kocher forceps are usually enough. One or two other artery forceps, a pair of Farabeuf retractors and a scalpel may be useful for a contused or deep wound. Instruments to suture one wound for one patient must be packaged and sterilised together (suture box or set) to limit handling and breaks in asepsis. Renewable supplies For local anaesthesia: sterile syringe and needle; 1% lidocaine (without epinephrine)
Sterile gloves, fenestrated sterile towel Antiseptic and supplies for dressings
256
Technique
Settle the patient comfortably in an area with good lighting and ensure all the necessary material is prepared. Explain the procedure to the patient and ensure his co-operation. If the patient is a young child, arrange to have an assistant hold the child if necessary. Initial cleaning
Wear suitable clothing: sterile gloves for all wounds and a gown and protective glasses if there is a risk of projection from a bleeding wound.
If necessary use a sterile brush. Cleaning with running water is preferable to cleaning by immersion.
Start by washing the wound, prolong the cleaning if the wound is particularly soiled. Use ordinary soap or polyvidone iodine scrub solution and water and rinse.
If the wound is infected and the patient has general signs of infection (fever, chills, changes in the overall condition) systemic antibiotic therapy may be required. Administer antibiotics at least one hour prior to starting care. Exploration Wash hands and put on sterile gloves.
Local anaesthetic: infiltrate 1% lidocaine into the edges of the wound and wait at least 2 minutes for the anaesthetic to take effect.
Disinfect the wound and surrounding area with 10% polyvidone iodine.
Proceed carefully from the superficial to the deepest parts of the wound to explore the extent of the wound, if necessary, aided by an assistant.
Consider the anatomical location of the wound and look for injury to any underlying structures (the clinical examination of a limb must include evaluation of sensitivity and motor functioning, as well as that of tendons in order to orient surgical exploration): a wound that communicates with a fracture is an open fracture, a wound close to a joint may be a joint wound, a wound on the hands or feet may affect the nerves and/or tendons. Look for and remove any foreign bodies. In the event of significant pain or bleeding, the exploration must be completed in an operating room.
10
257
Wound excision
The goal of the excision is to remove non-viable tissue, which favours the proliferation of bacteria and infection. The wound may require little or no excision if it is clean. The excision is more extensive if the wound is bruised, irregular or extensive. Limit excision of the skin around the wound, particularly in facial wounds. Sub-cutaneous fat and tissue of doubtful viability should be generously excised in order to leave only well vascularised tissue. Immediate suturing of a simple wound
Immediate suturing may have serious consequences for the patient if precautions to prevent infection and promote healing are not taken.
The decision to suture immediately can only be taken after the cleaning, exploration and satisfactory excision, and if the following conditions are met: simple wound, no more than 6 hours old with no devitalised or contused tissue (the wound may be as long as 24 hours old if on the face, scalp, upper limbs or hands). Bites (for local treatment see Rabies, page 194) and bullet, shell or mine shrapnel wounds should not be immediately sutured. Delayed suturing of a simple wound Wounds that do not fill the above conditions should not be immediately sutured.
After cleaning, exploration and excision a simple dressing is applied to the open wound. If after 72 hours there are no signs of local infection, the wound may be sutured. Healing by second intention of infected wounds
Further cleaning and removal of any remaining necrotic tissue is completed with daily dressing changes.
If the wound does not meet the conditions of cleanliness described above, the wound cannot be sutured. It will heal either spontaneously (healing by secondary intention), or will require a skin graft (once the wound is clean) if there is significant loss of tissue.
258
10
259
Figure 2a Always mount a surgical blade using a needle holder. Change the blade for each new procedure.
Figure 2b Dissecting forceps should not be held in the palm of the hand, but rather between the thumb and index finger. Toothed dissecting forceps should only be used on skin.
Figure 2c Insert the thumb and the ring finger into the handle of a needle holder (or scissors), and stabilize the instrument using the index finger. Figures 2: How to hold instruments
260
Figure 3a Debridement of a contused, ragged wound: straightening of the wound edges with a scalpel. Be conservative in facial wounds.
10
Figure 3c Excision of contused muscle Figures 3: Wound debridement This should be done sparingly, limited to excision of severely contused or lacerated tissue that is clearly becoming necrotic.
261
Figure 4a Loop the suture around the needle holder in one direction and remember the direction of the loop. Grasp the loose end with the needle holder and pull it through the loop to make the first knot. Lower the knot so that it closes the wound.
Figure 4b The second loop should be in the opposite direction. At least 3 knots are needed to make a suture, alternating from one direction to the other.
262
Figure 4e Figure 4f Grasp the loose end with the needle holder.
Figure 4g First flat knot Slide the knot towards the wound using the hand holding the loose end while holding the other end with the needle holder. Tighten the knot without causing tissue ischaemia.
10
Figure 5c Figure 5d The suture is too shallow, the edges are invaginated.
264
Figure 7: Closure of the skin, simple interrupted sutures with non-absorbable sutures
10
265
Burns
Burns
Burns are cutaneous lesions caused by exposure to heat, electricity, chemicals or radiation. They cause significant pain and may threaten survival and/or compromise function.
Classification of burns
Severe burns: one or more of the following parameters: Involving more than 10% of the body surface area (BSA) in children and 15% in adults Inhalation injury (smoke, hot air, particles, toxic gas, etc.) Major concomitant trauma (fracture, head injury, etc.) Location: face, hands, neck, genitalia/perineum, joints (risk of functional deficit) Electrical and chemical burns or burns due to explosions Age < 3 years or > 60 years or significant co-morbidities (e.g. epilepsy, malnutrition)
Minor burns: involving less than 10% of the BSA in children and 15% in adults, in the absence of other risk factors.
Evaluation of burns
Extent of burns
Location Head Neck Anterior trunk Right buttock Left buttock
Posterior trunk Perineum/genitalia Right upper arm Left upper arm Left lower arm Right hand Left hand Right leg Left leg Left foot Left thigh Right thigh Right lower arm
2.5 2.5
2.5 2.5
2.5 2.5
2.5 2.5
2.5 2.5
Right foot
266
This table helps to accurately calculate the % of BSA involved according to patients age: e.g. burn of the face, anterior trunk, inner surface of the lower arm and circumferential burn of left upper arm in a child 2 years of age: 8.5 + 13 + 1.5 + 4 = 27% BSA. Depth of burns Apart from first-degree burns (painful erythema of the skin and absence of blisters) and very deep burns (third-degree burns, carbonization), it is not possible, upon initial examination, to determine the depth of burns. Differentiation is possible after D8-D10.
Sensation Colour Texture Superficial burn on D8-D10 Pink, blanches with pressure Minimal fibrinous exudate Granulation tissue evident Bleeds when incised Smooth and supple Normal or pain Insensitive or diminished sensation White, red, brown or black Does not blanch with pressure Firm and leathery Deep burn on D8-D10
Appearance Healing
Very deep burn: always requires surgery (no spontaneous healing) Intermediate burn: may heal sponta neously in 3 to 5 weeks; high risk of infection and permanent sequelae
Dyspnoea with chest wall indrawing, bronchospasm, soot in the nares or mouth, productive cough, carbonaceous sputum, hoarseness, etc.
On admission
10
Burns
Assess for associated injuries (fractures, etc.). Protect the patient and keep him warm: clean/sterile sheet, survival blanket. Insert a urinary catheter if burns involve > 15% of BSA, and in the case of electrical burns or burns of the perineum/genitalia. Insert a nasogastric tube if burns involve > 20% of BSA (in the operating room while carrying out dressing procedure). Calculate and initiate fluid and electrolyte requirements for the first 24 hours. Intensive monitoring: level of consciousness, pulse, blood pressure, pulse oxymetry, respiratory rate (RR) hourly; temperature and urine output every 4 hours. Additional testing: haemoglobin, blood group, urine dipstick test. Prepare the patient for the first dressing procedure in the operating room.
Notes: Burns do not bleed in the initial stage: check for haemorrhage if haemoglobin level is normal or low. Burns alone do not alter the level of consciousness. In the case if altered consciousness, consider head injury, intoxication, postictal state in epileptic patients. Clinical manifestations of electrical burns vary significantly according to the type of current. Look for complications (arrhythmia, rhabdomyolysis, neurological disorders).
Fluid and electrolyte requirements during the first 48 hours according to age
2 ml/kg x % BSA of RL + maintenance fluid* per hour x 8 h 2 ml/kg x % BSA of RL 2 ml/kg x % BSA of RL Children 12 years/adults
0-8h
8 - 24 h
24 - 48 h
* maintenance fluid: alternate RL and 5% glucose: 4 ml/kg/h for first 10 kg of body weight + 2 ml/kg/h for next 10 kg + 1 ml/kg/h for each additional kg (over 20 kg, up to 30 kg)
Daily maintenance IV fluid requirements* 40 ml/kg RL minus oral fluids (do not minus oral fluids such as milk, broth, include drinking water in the calculation). gavage feeds (do not include drinking water in the calculation).
Note: increase replacement volumes by 50% (3 ml/kg x % BSA for the first 8 hours) in the event of inhalation injury or electrical burn. For burns > 50% BSA, limit the calculation to 50% BSA.
This formula provides a guide only and should be adjusted according to systolic arterial pressure (SAP) and urine output. Avoid fluid overload. Reduce replacement fluid volumes if urine output exceeds the upper limit.
268
AP (mmHg)
Stop the infusion after 48 hours, if fluid requirements can be met by the oral route or gavage. Respiratory care In all cases: continuous inhalation of humidified oxygen, chest physiotherapy. Emergency surgical intervention if necessary: tracheotomy, chest escharotomy. Do not administer corticosteroids (no effect on oedema; predisposition to infection). No specific treatment for direct bronchopulmonary lesions. Analgesia Nutrition See Pain management, page 271. Start feeding early, beginning at H8: Daily needs in adults: calories: 25 kcal/kg + 40 kcal/% SCB proteins: 1.5 to 2 g/kg High energy foods (NRG5, Plumpy'nut, F100 milk) are necessary if the BSA is > 20% (normal food is inadequate). Nutritional requirements are administered according to the following distribution: carbohydrates 50%, lipids 30%, proteins 20%. Provide 5-10 times the recommended daily intake of vitamins and trace elements. Enteral feeds are preferred: oral route or nasogastric tube (necessary if BSA > 20%). Start with small quantities on D1, then increase progressively to reach recommended energy requirements within 3 days. Assess nutritional status regularly (weigh twice weekly). Reduce energy loss: occlusive dressings, warm environment (28-33C), early grafting; management of pain, insomnia and depression. Monitor for myoglobinuria: dark urine and urine dipstick tests. If present, induce alkaline diuresis for 48 hours (20 ml of 8.4% sodium bicarbonate per litre of RL) to obtain an output of 1 to 2 ml/kg/h. Do not administer dopamine or furosemide. Patients at risk of rhabdomyolysis (deep and extensive burns, electrical burns, crush injuries to the extremities)
Urine output
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269
Burns
Control of infection
Precautions against infection are of paramount importance until healing is complete. Infection is one of the most frequent and serious complications of burns: Follow hygiene precautions (e.g. sterile gloves when handling patients). Rigorous wound management (dressing changes, early excision). Separate new patients (< 7 days from burn) from convalescent patients ( 7 days from burn). Do not administer antibiotherapy in the absence of systemic infection. Infection is defined by the presence of at least 2 of 4 following signs: temperature > 38.5C or < 36C, tachycardia, tachypnoea, elevation of white blood cell count by more than 100% (or substantial decrease in the number of white blood cells). In the event of systemic infection, start empiric antibiotic treatment: Children > 1 month: cefazolin IV: 75 mg/kg/day in 3 injections + ciprofloxacin PO: 30 mg/kg/day in 2 doses Adults: cefazolin IV: 6 g/day in 3 injections + ciprofloxacin PO: 1.5 g/day in 3 doses Local infection, in the absence of signs of systemic infection, requires topical treatment with silver sulfadiazine. Omeprazole IV from D1: Children: 1 mg/kg once daily Adults: 40 mg once daily Tetanus immunization/prophylaxis (see Tetanus, page 170). Thromboprophylaxis: nadroparin SC beginning 48 to 72 h post-injury. High risk dosing protocol if the BSA is > 50% and/or in the event of high-voltage electrical injury; moderate risk dosing protocol if the BSA is 20 to 50% and/or in the event of burns of the lower limbs. Physiotherapy from D1 (prevention of contractures), analgesia is necessary. Intentional burns (suicide attempt, aggression): appropriate psychological follow-up. Other treatments
Regular dressing changes1 prevent infection, decrease heat and fluid losses, reduce energy loss, and promote patient comfort. Dressings should be occlusive, assist in relieving pain, permit mobilisation, and prevent contractures.
Basic principles Rigorous adherence to the principles of asepsis. Dressing changes require morphine administration in the non-anaesthetised patient. The first dressing procedure is performed in the operating room under general anaesthesia, the following in an operating room under general anaesthesia or at the bedside with morphine.
1 Open technique naked burn patient under a mosquito net and water immersion therapy are obsolete and
Technique At the time of the first dressing procedure, shave any hairy areas (armpit, groin, pubis) if burns involve the adjacent tissues; scalp (anteriorly in the case of facial burns, entirely in the case of cranial burns). Cut nails. Clean the burn with polyvidone iodine scrub solution (1 volume of 7.5% PVI + 4 volumes of 0.9% sodium chloride or sterile water). Scrub gently with compresses, taking care to avoid bleeding.
should no longer be used.
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Frequency: routinely every 48 hours; daily in the event of superinfection or in certain areas (e.g. perineum). Monitoring Distal ischaemia of the burned limb is the main complication during the first 48 hours. Assess for signs of ischaemia: cyanosis or pallor of the extremity, dysaesthesia, hyperalgia, impaired capillary refill. Monitor daily: pain, bleeding, progression of healing and infection.
Remove blisters with forceps and scissors. Rinse with 0.9% sodium chloride or sterile water. Dry the skin by blotting with sterile compresses. Apply silver sulfadiazine directly by hand (wear sterile gloves) in a uniform layer of 3-5 mm to all burned areas (except eyelids and lips). Apply a greasy dressing (Jelonet or petrolatum gauze) using a to-and-fro motion (do not use circular dressings). Cover with a sterile compresses, unfolded into a single layer. Never encircle a limb with a single compress. Wrap with a crepe bandage, loosely applied. Elevate extremities to prevent oedema; immobilise in extension.
Emergency surgical interventions: Escharotomy: in the case of circumferential burns of arms, legs or fingers, in order to avoid ischaemia, and circumferential burns of chest or neck that compromise respiratory movements. Tracheotomy: in the event of airway obstruction due to oedema (e.g. deep cervicofacial burns). Tracheotomy can be performed through a burned area. Tarsorrhaphy: in the event of ocular or deep eyelid burns. Surgery for associated injuries (fractures, visceral lesions, etc.).
Burn surgery: Excision-grafting of deep burns, in the operating room, under general anaesthesia, between D5 and D6: excision of necrotic tissue (eschar) with simultaneous grafting with autografts of thin skin. This intervention entails significant bleeding risk, do not involve more than 15% of BSA in the same surgery. If early excision-grafting is not feasible, default to the process of sloughinggranulation-re-epithelisation. Sloughing occurs spontaneously due to the action of sulfadiazine/petrolatum gauze dressings and, if necessary, by mechanical surgical debridement of necrotic tissue. This is followed by granulation, which may require surgical reduction in the case of hypertrophy. The risk of infection is high and the process is prolonged (> 1 month).
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V. Pain management
All burns require analgesic treatment. Pain intensity is not always predictable and regular assessment is paramount: use a simple verbal scale (SVS) in children > 5 years and adults and NFCS or FLACC scales in children < 5 years (see Pain, page 29).
271
Burns
Morphine is the treatment of choice for moderate to severe pain. Development of tolerance is common in burn patients and requires dose augmentation. Adjuvant treatment may complement analgesic medication (e.g. massage therapy, psychotherapy). Continuous pain (experienced at rest) Moderate pain: paracetamol PO: 60 mg/kg/day in 4 divided doses + tramadol PO: 4 to 8 mg/kg/day in 4 divided doses
Moderate to severe pain: paracetamol PO: 60 mg/kg/day in 4 divided doses + slow release morphine PO: 1 to 2 mg/kg/day in 2 divided doses at 12 hour-interval. In patients with severe burns, oral drugs are poorly absorbed in the digestive tract during the first 48 hours. Morphine must be administered by SC route: 0.2 mg/kg every 4 hours. Acute pain experienced during care Analgesics are given in addition to those given for continuous pain. Significant medical interventions and extensive burns: general anaesthesia in an operating room. Limited non-surgical interventions (dressings, painful physiotherapy): Mild to moderate pain, 60 to 90 minutes before giving care: codeine PO: 0.6 mg/kg or tramadol PO: 2 mg/kg rarely allows treatment to be completed comfortably. In the event of treatment failure, use morphine. Moderate or severe pain, 60 to 90 minutes before giving care: immediate release morphine PO: initial dose of 0.5 to 1 mg/kg. The effective dose is usually around 1 mg/kg, but there is no maximum dose. or morphine SC: initial dose of 0.2 to 0.5 mg/kg. The effective dose is usually around 0.5 mg/kg, but there is no maximum dose.
Note: doses given are for adults. For paracetamol, dosing is the same in children. For tramadol and codeine, dosing is the same in children > 6 months. For morphine, dosing is the same in children > 1 year, should be halved in children less than 1 year, and quartered in infants less than 3 months.
Pain management using morphine during dressing changes at the bedside requires: A trained nursing team. Availability of immediate release oral morphine and naloxone. Close monitoring: level of consciousness, RR, pulse, SaO2, every 15 min for the first hour following dressing change, then routine monitoring. Assessment of pain intensity and sedation during the intervention and for 1 hour thereafter. Necessary equipment for ventilation by mask and manual suction. Gentle handling of the patient at all times.
Adjustment of morphine doses for subsequent dressings: If pain intensity (SVS) is 0 or 1: continue with the same dose. If SVS score 2: increase the dose by 25 to 50%. If pain control remains inadequate, the dressing change should be carried out in the operating room under anaesthesia. Take advantage of the residual analgesia following dressing changes to carry out physiotherapy. As a last resort (morphine unavailable and no facilities to give general anaesthesia), in a safe setting (trained staff, resuscitation equipment, recovery room), adding ketamine IM at analgesic doses (0.5 to 1 mg/kg) reinforces the analgesic effect of the paracetamol + tramadol combination given before a dressing change.
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The treatment is guided by self-evaluation of pain intensity, and utilises paracetamol and/or tramadol. Patients may develop neuropathic pain (see treatment page 35). All other associated pain (physiotherapy, mobilization) should be treated as acute pain.
Wound care: dressings with silver sulfadiazine or petrolatum gauze (except for firstdegree superficial burns). Pain: paracetamol tramadol usually suffices.
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273
Abscesses
Abscesses
An abscess is a collection of pus in the soft tissues most commonly due to Staphylococcus aureus. During the suppurative stage, a ripe abscess is red, inflamed, painful, shiny and swollen. It is usually fluctuant on palpation and may be fistulated. At this stage, the abscess cavity is inaccessible to antibiotics and surgical drainage is the only effective treatment. During the early indurated stage, that precedes the suppurative stage medical treatment may be effective.
Treatment
Apply compresses soaked in 70% alcohol, 2 times/day (maximum 3 times/day to prevent burns to the skin). If there is improvement after 48 hours: continue antibiotic treatment for 5 days to complete 7 days of treatment. If there is no improvement after 48 hours of correct treatment: treat surgically.
Antibiotic therapy: Children: amoxicillin PO: 80 mg/kg/day in 3 divided doses + metronidazole PO: 30 to 50 mg/kg/day in 3 divided doses Adults: amoxicillin PO: 3000 mg/day in 3 divided doses + metronidazole PO: 1500 mg/day in 3 divided doses or amoxicilline/clavulanic acid (co-amoxiclav) PO, only if formulations in a ratio 8:1 or 7:1 are available. The dose is expressed in amoxicillin: Children < 40 kg: 80 mg/kg/day in 2 to 3 divided doses Children 40 kg and adults: 2500 to 3000 mg/day in 3 divided doses depending on formulation available: - ratio 8:1 : 3000 mg/day = 2 tablets of 500/62.5 mg, 3 times/day - ratio 7:1 : 2625 mg/day = 1 tablet of 875/125 mg, 3 times/day
Material
Sterile scalpel handle and blade Sterile curved, non-toothed artery forceps (Kelly type) Sterile gloves Antiseptic 5 or 10 ml syringe Non-absorbable sutures Sterile corrugated drain
274
Anaesthesia
With the exception of paronychia, local anaesthesia of the abscess is usually impossible. General anaesthesia may be indicated, using: ketamine IM: 10 mg/kg
Technique
Hold the scalpel between the thumb and middle finger of the dominant hand, the index finger presses on the handle. Hold the abscess between the thumb and index finger of the other hand. The scalpel blade should be perpendicular to the skin. The incision is made in a single stroke along the long axis of the abscess. The incision must be long enough for a finger to be inserted. Be cautious when excising an abscess located over a blood vessel (carotid, axillary, humeral, femoral, popliteal). Explore the cavity with the index finger, breaking down all loculi (a single cavity should remain), evacuate the pus and explore to the edges of the cavity.
Washing
The exploration also allows an assessment of the extent of the abscess, the depth, and location with respect to underlying structures (arterial pulsation) or any possible contact with underlying bone. In this last case, seek surgical advice. Abundant washing of the cavity using a syringe filled with antiseptic solution. Insert a drain (or, failing that a gauze wick) into the base of the cavity. If possible, fix it to the edge of the incision with a single suture. The drain is withdrawn progressively and then, after 3 to 5 days removed completely.
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Abscesses
Apply a constrictive bandage, stop breast-feeding from the infected breast; express milk using a breast pump to avoid engorgement.
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Incision: radial for superficial abscesses, peri-areolar for abscesses near the nipple, submammary for deep abscesses. Gentle exploration with a finger. Insert a corrugated drain.
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277
Abscesses
Parotid abscess
There is a risk of severing the facial nerve when incising a parotid abscess. The incision should be horizontal along the lower margin of the abscess.
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Pyomyositis
Pyomyositis is an infection of the muscle, almost always due to Staphylococcus aureus. It most commonly affects the muscles of the limbs and torso. These infections may occur simultaneously in multiple sites. During the early indurated stage, while the muscle is swollen, hot and painful, medical treatment may be effective. During the suppurative stage, when the abscess has formed, surgical drainage is the only effective treatment.
Treatment
Immobilise the limb. Antibiotic therapy as for other abscesses (see page 274). Adapt analgesics to the pain level (see Pain, page 29). Apply compresses soaked in 70% alcohol, 2 times/day (maximum of 3 times/day to prevent burns to the skin).
Treatment of pyomyositis is by incision following the rules for incision of abscesses described on page 275. Muscle abscesses are often deeper than other abscesses. As a result, needle aspiration with a large bore needle may be necessary to locate the abscess; it yields thick pus. Needle aspiration is insufficient treatment even if pus is evacuated.
As for abscesses (see pages 274 and 275). Generous incision along the axis of the limb, over the site of the abscess and avoiding underlying neurovascular stuctures; incise the skin, subcutaneous tissues and muscular fascia with a scalpel (Figure 11a). Dissect the muscle fibres with non-toothed forceps (Kelly type) or round tipped scissors. Insert the instrument into the muscle until the purulent cavity is reached. During insertion, keep the instrument closed and perpendicular to the muscle fibres. Withdraw gently with the scissors or forceps slightly open, keeping instrument perpendicular to the fibres (Figure 11b). Use a forefinger to explore the cavity, break down any loculi and evacuate the pus (Figure 11c). Wash abundantly with antiseptic solution. Insert a large drain. Fix the drain to the edge of the wound using a single suture. Remove the drain on about the 5th day (Figure 11d).
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Technique
10
Pyomyositis
Special site
Myositis of the psoas muscle: if the abscess is on the right side, the clinical signs are the same as for appendicitis with pain in the right iliac area. Transfer the patient to a surgical centre.
Figure 11b Dissection of the muscle using Kelly forceps, insert closed then withdraw with the instrument slightly open
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Leg ulcers
Leg ulcers are chronic losses of cutaneous tissue. They are common in tropical regions, resulting from varied aetiologies: vascular: venous and/or arterial insufficiency bacterial: leprosy, Buruli ulcer (Mycobacterium ulcerans), phagedenic ulcer, yaws, syphilis parasitic: dracunculiasis (Guinea-worm disease), leishmaniasis metabolic: diabetes traumatic: trauma is often a precipitating factor combined with another underlying cause The history of the disease and a complete clinical examination (paying particular attention to the neurological examination to determine if there is a peripheral neuropathy caused by leprosy or diabetes) usually leads to an aetiological diagnosis. All ulcers may become complicated with either local or regional secondary infections (abscess, lymphadenopathy, adenitis, osteomyelitis, erysipela, pyodermitis), generalised infection (septicaemia), tetanus and after many years of evolution, skin cancer.
Remove any necrotic (black) and fibrinous (yellowish) tissue using compresses or excise the tissue with a scalpel. Apply: to a clean ulcer, with little discharge: 10% polyvidone iodine and vaseline; to a dirty ulcer, with little discharge: silver sulfadiazine; to an oozing ulcer: 10% polyvidone iodine alone; to multiple or extensive ulcers with no discharge: silver sulfadiazine (monitor for systemic adverse effects); to multiple or extensive oozing ulcers: diluted polyvidone iodine ( 1/4 of 10% polyvidone + 3/4 of 0.9% NaCl or clean water) for one minute then rinse with 0.9% NaCl or clean water to reduce the risk of transcutaneous iodine absorption. Cover with a dry sterile dressing.
Bathe the leg for 10 to 15 minutes in NaDCC or chloramine and rinse in boiled water.
10
Systemic treatment
Treatment with analgesics in the event of pain: adapt the level and dosage to the individual (see Pain, page 29). Give systemic antibiotics in case of: secondary infection (see Bacterial skin infections, page 105).
281
Leg ulcers
phagedenic ulcer (in the early stages, antibiotics may be useful. They are often ineffective in the chronic stages):
benzylpenicillin procaine + benzylpenicillin IM (if necessary give half the dose in each buttock) Children: 100 000 IU/kg once daily for 7 days Adults: 4 MIU once daily for 7 days
If the patient is allergic to penicillin: erythromycin PO Children: 50 mg/kg/day in 2 divided doses Adults: 2 g/day in 2 divided doses or doxycycline PO (except in children under 8 years and pregnant or lactating women) Children over 8 years: 4 mg/kg once daily Adults: 200 mg once daily or metronidazole PO Children: 30 mg/kg/day in 3 divided doses Adults: 1.5 g/day in 3 divided doses
If after 7 days the choosen antibiotic shows to be effective, continue for as long as needed, treatment duration varies according to the clinical evolution. For patients treated with penicillin, change to oral treatment after 7 days by using phenoxymethylpenicillin PO Children from 1 to 5 years: 500 mg/day in 4 divided doses Children from 6 to 12 years: 1 g/day in 4 divided doses Adults: 2 g/day in 4 divided doses
Complementary therapy: Elevate the legs in cases of venous and/or lymphatic insufficiency Give tetanus prophylaxis if appropriate (see Tetanus, page 170) Skin graft 1 if the ulcer is extensive, clean, red and flat. Skin grafts are often necessary after surgical excision to heal phagedenic and Buruli ulcers.
1 For techniques of skin grafting, refer to the MSF handbook, Minor surgical procedures in remote areas.
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It is rare that the snake involved is identified. However, observation of the clinical signs may orient diagnosis and management. Two major syndromes are identified: neurological disorders that evolve towards respiratory muscle paralysis and coma are common manifestations of elapid envenomation (cobra, mamba, etc.); extensive local lesions (intense pain, inflammation with oedema and necrosis) and coagulation abnormalities are common manifestations of viperid or crotalid (rattle snake) envenomation. Clinical manifestations and management of bites and envenomations are described in the following page. Early diagnosis and monitoring of coagulation abnormalities is based on whole blood clotting tests performed in a dry tube (at the patients arrival and then every 4 to 6 hours for the first day). Take 2 to 5 ml of whole blood, wait 30 minutes and examine the tube: Complete clotting: no coagulation abnormality Incomplete clotting or no clotting: coagulation abnormality, susceptibility to bleeding1 In the event of coagulation abnormalities, continue to monitor once daily until coagulation returns to normal.
Aetiological treatment is based on the administration of snake antivenom serum, only if there are clear clinical manifestations of envenomation or coagulation abnormalities are observed. Antivenom sera are effective, but rarely available (verify local availability) and difficult to store. Antivenom serum should be administered as early as possible: by IV infusion (in 0.9% sodium chloride) if using a poorly purified serum; by slow IV in the event of severe envenomation if the serum is known to be well purified. Repeat antivenom serum administration after 4 or 6 hours if the symptoms of envenomation persist. For all patients, be prepared for an anaphylactic reaction, which, despite its potential severity (shock), is usually more easily controlled than coagulation disorders or serious neurological disorders.
10
In asymptomatic patients (bites without signs of envenomation and with normal coagulation), monitoring must continue for at least 12 hours (24 hours preferred).
1 There can be a considerable delay between the decrease in coagulation factors (less than 30 minutes after the
bite) and the first signs of bleeding (other than bleeding at the site of the bite and/or the development of serosanguinous blisters), which may appear only 3 days after the bite. Conversely, bleeding may resolve prior to normalization of coagulation parameters. 283
Clinical manifestations
Fang marks Pain at the site of bite
Treatment
Strict rest, immobilisation of the limb with a splint to slow the diffusion of venom2. Wound cleansing. Tetanus prophylaxis, page 170. Observe for manifestations of envenomation. A the dispensary level, prepare patient evacuation to a referral centre. Insert a peripheral IV line. IV antivenom serum as soon as possible.
10-30 minutes Hypotension, myosis, excessive salivation and sweating, dysphagia, dyspnoea Local paraesthesia, paresis Inflammatory syndrome: intense pain, extensive regional oedema
Envenomation
Elapids
Cobra syndrome: bilateral eyelid drooping, trismus, respiratory muscle paralysis Shock
Insert a peripheral IV line. IV antivenom serum as soon as possible. Analgesics3. IV or PO3 anti-inflammatories. See Shock, page 17.
Haemorrhagic syndome: Viperids epistaxis, purpura, haemolysis Crotalids or disseminated intravascular coagulation Shock No signs or changes in coagulation (non-venomous snakes or snake bite without envenomation) Tissue necrosis ?
Monitor coagulation (blood clotting test in a dry tube). Transfusion of fresh blood in the event of severe anaemia. See Shock, page 17. Reassure the patient. Send him home after 12 hours.
2 Tourniquets, incision-suction and cauterisation are ineffective and may be dangerous. 3 Do not use acetylsalicylic acid (aspirin).
In case of clinical evidence of infection only: drainage of any abscess; amoxicillin/clavulanic acid (co-amoxiclav) for 7 to 10 days in case of cellulitis. Infections are relatively rare, and most often associated with traditional treatment or with nosocomial transmission after unnecessary or premature surgery.
Remove blisters, clean; daily (non occlusive) dressings. Surgical intervention for necrosis, depending on the extent, after the lesions stabilise (minimum 15 days).
284
10
Local care: remove the embedded sting (bee), clean with soap and water; if pruriginous, apply calamine lotion.
In the event of an anaphylactic reaction: epinephrine (adrenaline) IM Use undiluted epinephrine solution (1:1000 = 1 mg/ml) and a 1 ml syringe graduated in 0.01 ml in children: Children under 6 years: 0.15 ml Children from 6 to 12 years: 0.3 ml Children over 12 years and adults: 0.5 ml For children, if 1 ml syringe is not available, use a diluted solution, i.e. add 1 mg epinephine to 9 ml of 0.9% sodium chloride to obtain a 0.1 mg/ml solution (1:10 000): Children under 6 years: 1.5 ml Children from 6 to 12 years: 3 ml Repeat after 5 minutes if no clinical improvement. Use IV epinephrine (for doses, see Anaphylactic shock , page 19) in patients with circulatory collapse or those who deteriorate despite receiving IM epinephrine.
286
Dental infections
Infection arising as a secondary complication of an inflammation of the dental pulp. The severity and the treatment of dental infections depend on their evolution: localised to the infected tooth, extended to adjacent anatomical structures or diffuse infections.
Clinical features and treatment Infection localised to a tooth and its surroundings (acute dental abscess)
Intense and continuous pain. On examination: swelling limited to the gum surrounding the infected tooth. Purulent exudate may be present draining either through the root canal, or through the periodontal ligament (loosening the tooth) or through a gingival fistula. There are no signs of the infection extending to adjacent anatomical structures nor general signs of infection. Treatment: Treatment is only surgical (the source of infection is inaccessible to antibiotics): root canal therapy (disinfection of the root canal) if possible or extraction of the tooth.1 Pain: paracetamol or ibuprofen PO (see Pain, page 29).
Local spreading of an acute dental abscess into the surrounding bone and tissue.
Painful gingival and buccal swelling with warm and tender skin, developing into a ripe abscess: intense pain, with trismus, particularly if the infection is in a posterior tooth, presence of general signs (fever, fatigue, cervical lymphadenopathy). Treatment: First surgical: incision and drainage of the pus or extraction of the tooth.1 Then antibiotic treatment for 5 days following the procedure: amoxicillin PO Children: 50 mg/kg/day in 2 divided doses Adults: 2 g/day in 2 divided doses Notes: If the dental procedure has to be delayed (local anaesthesia not possible due to inflammation, significant trismus), start with antibiotic treatment, but the dental procedure must be completed in the following days. If there is no improvement within 48 to 72 hours after the dental procedure, do not change antibiotic, but start a new procedure on the tooth. Pain: paracetamol or ibuprofen PO (see Pain, page 29).
1 For techniques of dental extraction, see the MSF handbook, Minor surgical procedures in remote areas.
In patients with acute gangrenous cellulitis (crepitations on palpation), treat as an infection extending into the cervico-facial tissues (following page).
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287
Dental infections
Extremely serious cellulitis, with rapidly spreading cervical or facial tissue necrosis and signs of septicaemia. Treatment: treatment in an intensive care unit. high dose antibiotic treatment (see antibiotic treatment of septic shock, page 20). extraction of the tooth.2
2 For techniques of dental extraction, see the MSF handbook, Minor surgical procedures in remote areas.
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CHAPTER 11
Agitation
11
Anxiety
A patient suffering from anxiety has: psychical symptoms: pervasive worries, e.g. fear of having a serious illness, fear with no clearly-defined object or phobias; behavioural changes: nervousness, avoidance behaviour; physical symptoms: e.g., dry mouth, lump in the throat, nonspecific complaints (e.g. feeling of malaise, hot flashes or chills, diffuse pain).
Anxiety is a common feature in depression (page 297), post-traumatic stress disorder (page 295) and psychosis (page 300). It can also occur in isolation, not associated with any other mental disorders. Anxiety disorders often occur immediately after a difficult life event.
Management
Try to determine the source of the anxiety and reassure the patient. If necessary, use simple relaxation techniques to alleviate the symptoms1.
Severe anxiety may justify a short course2 (one to two weeks max.) of diazepam PO: 5 to 10 mg/day in 2 divided doses; reducing the dose by half in the last few days of treatment. If symptoms recur after treatment discontinuation, do not resume diazepam. Haloperidol PO at very low dose and for a short period of time (1 mg/day in 2 divided for maximum 2 to 4 weeks) may be used for its anxiolytic properties if a treatment is still needed. However, before prescribing haloperidol, re-evaluate for possible depression or post-traumatic stress disorder (see pages 295 and 297). For recurring attacks (panic disorder), clomipramine PO may be prescribed to prevent recurrences: 25 mg once daily, to be gradually increased to 75 mg once daily. Continue for 2 to 3 months after symptoms resolve then, stop gradually (over 3 to 4 weeks) while monitoring the patient for recurrence of symptoms.
If symptoms are exacerbated (e.g., tachycardia, feeling of suffocation, fear of dying or going crazy, agitation, or conversely, prostration), it may be necessary to administer diazepam: 5 to 10 mg PO or 10 mg IM, to be repeated after one hour if required.
For generalised anxiety, an antidepressant with anxiolytic properties is preferred (paroxetine PO: 10 to 20 mg maximum once daily at bedtime), to be continued for 2 to 3 months after symptoms resolve then, stop gradually over 2 weeks.
11
1 For example, in case of hyperventilation, use a technique that controls the respiratory rate: get the patient in a
comfortable position with his eyes closed. Help him focus on his breathing so that it becomes calmer and more regular, with three-phase breathing cycles: inhalation (count to three), exhalation (count to three), pause (count to three), etc. 2 Treatment should be short as benzodiazepines can cause dependence and tolerance. 291
Insomnia
Insomnia
Complaints may be: difficulty falling or remaining asleep, waking up too early in the morning, nightmares, or daytime fatigue.
Management
If the insomnia is related to an organic cause, treat the cause (e.g., administer analgesics for pain). If the insomnia is related to a particular life event (e.g. bereavement), a short term treatment with a sedating antihistamine (promethazine PO: 25 mg once daily at bedtime for 8 to 10 days) may be useful. If the insomnia is related to the use of alcohol, drugs or a medication1, management depends on the substance responsible.
If the insomnia persists, re-evaluate the patient. Insomnia is a common feature in depression (page 297), post-traumatic stress disorder (page 295) and anxiety disorders (page 291). In such cases, the underlying disorder should be addressed.
1 The main drugs known to cause sleep problems are corticosteroids, beta blockers, levodopa/carbidopa,
292
Agitation
Patients with anxiety or psychotic or personality disorders, or mental confusion may have periods of psychomotor agitation. Agitation is also common in acute intoxication (alcohol/drugs) and withdrawal syndrome (e.g. delirium tremens or abrupt interruption of antidepressant therapy). It may be accompanied by oppositional behaviour, violence or fleeing. Clinical evaluation is best performed in pairs, in a calm setting, with or without the persons family/friends, depending on the situation. It may be necessary to administer diazepam 10 mg PO to reduce the agitation and conduct the clinical exam.
Management
If the patient is violent or dangerous, urgent sedation is required: diazepam IM 10 mg, to be repeated after 30 to 60 minutes if necessary. Physical restraint may be required in certain circumstances. However, its use should be view as a temporary measure, always in combination with sedation and close medical supervision. Determine whether or not the patient is confused; look for an underlying cause, e.g., neurological, metabolic, etc. (see page 294). Management depends on the underlying cause. If the agitation is associated with anxiety, see page 291; if associated with psychotic disorders, see page 300.
In case of delirium tremens (DT): Admit the patient to an intensive care unit. Administer diazepam IV: 10 to 20 mg 4 to 6 times/day, under close supervision with ventilation equipment near at hand. The goal is to achieve mild sedation without provoking respiratory depression. The doses and duration of the treatment are adapted according to the clinical progress. Add chlorpromazine IM if necessary: 25 to 50 mg 1 to 3 times/day. IV hydration: 2 to 4 litres 0.9% sodium chloride/24 hours. Administer thiamine IM: 100 mg/day for at least 3 days. Monitor vital signs and blood glucose levels.
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Pre-DT symptoms can be prevented or treated with: diazepam PO (40 mg/day in 4 divided doses 6 hours apart for 1 to 3 days, then reduce and stop over 7 days) + oral hydration (3 litres of water/day) + thiamine IM (100 mg/day for at least 3 days). In post-operative patients, start with the parenteral route: diazepam slow IV, 5 to 10 mg 4 times daily (for precautions, see delirium tremens below) + IV hydration (2 to 4 litres 0.9% sodium chloride/24 hours) + thiamine IM as above.
Alcoholic patients can experience withdrawal symptoms within 6 to 24 hours after they stop drinking. In the early phase (pre-delirium tremens), the manifestations include irritability, a general feeling of malaise, profuse sweating and shaking. Withdrawal syndrome should be taken into consideration in patients who are hospitalised and therefore forced to stop drinking abruptly. At a more advanced stage (delirium tremens), agitation is accompanied by fever, mental confusion and visual hallucinations (zoopsia).
11
Mental confusion
Mental confusion
The clinical picture includes: disorientation in time and space; impaired consciousness; concentration problems; memory impairment. These symptoms develop rapidly (hours or days), and often fluctuate during the course of the day. Agitation, delusions, behavioural disorders and hallucinations (often visual) may complicate the picture.
Mental confusion almost always has an organic cause: Infectious: meningitis, cerebral malaria, encephalitis, septicaemia, syphilis, AIDS, etc. Metabolic: hyper/hypoglycaemia, electrolyte imbalance, niacin or B1 deficiencies, etc. Endocrine: thyroid disorders Neurological: epilepsy, raised intracranial pressure, head trauma, meningeal haemorrhage, brain tumour, etc. Also consider treatment adverse effects (corticosteroids, opioid analgesics, psychotropic drugs, etc.), use of toxic substances (alcohol/drugs), or withdrawal from these substances (see delirium tremens, page 293).
Management
294
Post-traumatic stress disorder (PTSD) is characterised by three types of psychological response, generally seen in combination:
Increased arousal Constant state of alert, exaggerated startle response, anxiety, insomnia, poor concentration. The patient may develop somatic symptoms such as hypertension, sweating, shaking, tachycardia, headache, etc.). Re-experiencing is highly distressing and causes disorders that may worsen over time; people isolate themselves, behave differently, stop fulfilling their family/social obligations, and experience diffuse pain and mental exhaustion.
Management
Psychological intervention is essential to reduce the suffering, disabling symptoms and social handicaps resulting from PTSD. It is important to reassure the patient that his symptoms are a comprehensible response to a very abnormal event. Sessions should be conducted with tact. The patient should be encouraged to talk about his experience. Avoid over active explorations of the patients emotions: leave it to the patient to decide how far he wants to go.
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295
Associated symptoms (anxiety or insomnia), if persistent, can be relieved by symptomatic treatment (diazepam) for no more than two weeks1. If the patient has severe symptoms (obsessive thoughts, pronounced arousal, etc.), the pharmacological treatment is paroxetine PO (see page 291).
1 Benzodiazepines can lead to dependence and tolerance. They should be used only for severe conditions and for a
296
Depression
Depression is characterised by a set of symptoms lasting at least two weeks and causing a change from the patients previous functioning. The classic diagnostic criteria for a major depressive episode are: Pervasive sadness and/or a lack of interest or pleasure in activities normally found pleasurable And At least four of the following signs: Significant loss of appetite or weight Insomnia, especially early waking (or, more rarely, hypersomnia) Psychomotor agitation or retardation Significant fatigue, making it difficult to carry out daily tasks Diminished ability to make decisions or concentrate Feeling of guilt or worthlessness, loss of self-confidence or self-esteem Feeling of despair Thoughts of death, suicidal ideation or attempt
The features of depression can vary, however, from one culture to another1. For example, the depressed patient may express multiple somatic complaints rather than psychological distress. Depression may also manifest itself as an acute psychotic disorder in a given cultural context.
Management
When faced with symptoms of depression, consider an underlying organic cause (e.g., hypothyroidism or Parkinsons disease) or adverse effects from medical treatment (corticosteroids, cycloserine, efavirenz, levodopa, etc.). Look for a triggering event (e.g. rape, recent childbirth and post-partum depression). Depressive symptoms are the most common psychical disorders in patients with severe chronic infectious diseases such as HIV infection or tuberculosis. These symptoms should not be neglected, especially as they have a negative impact on adherence to treatment.
Symptoms of depression are usual right after a major loss (bereavement, exile, etc.). They gradually subside, in most cases, with support from relatives. Psychological support may be useful. Pharmacological treatment is justified if there is a risk of suicide or in the event of severe or long-lasting problems with significant impact on daily life, or if psychological follow-up alone is not enough. Before prescribing, make sure that a 6-month treatment and follow-up (psychological support, adherence and response) is possible.
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1 Hence the importance of working with an informant (in the anthropological sense of the word) when dealing
297
Depression
Preferably use a serotonin reuptake inhibitor (SRI), particularly in elderly patients: paroxetine PO: 20 mg once daily in the evening or fluoxetine PO: 20 mg once daily in the morning; use with caution in patients with severe anxiety disorders or who are immobilised (e.g., wounded). If the depression is accompanied by severe anxiety, use amitriptyline PO instead: start with 25 mg once daily and gradually increase over one week to 75 mg once daily (150 mg/day maximum). Be careful with tricyclic antidepressants, as the therapeutic dose is close to the lethal dose. In elderly patients, reduce the dose by half.
Depression is less frequent in pregnancy than in the postpartum period. In situations where antidepressants are required, use paroxetine rather than fluoxetine if the woman plans to breastfeed. In the event of pregnancy in a woman under antidepressants, reevaluate the need to continue the treatment. If the treatment is still necessary, refer to the table below. Monitor newborns for signs of toxicity or withdrawal symptoms during the first few days of life.
Fluoxetine (mg/day)
Antidepressant therapy
Paroxetine (mg/day)
Amitriptyline (mg/day)
W1 20
W2 20
W3 20
M1 40
W1 20
W2 20
W3 20
M1 40
W1 25 25
W2 50 25
W3 75 50
M1 75
Increase at M1 (end of the first month) only if still necessary. Avoid Can be used Can be used
idem
idem
100
Breastfeeding Pregnancy
If SRIs are unavailable or poorly tolerated, clomipramide PO may also be use: start with 25 mg once daily at bedtime, and gradually increase over one week to 75 mg once daily (150 mg/day maximum).
There is a delay of 2 to 3 weeks before antidepressant effect occurs. During this period, anxiety may be exacerbated and the risk of suicide increased, especially with fluoxetine and clomipramine. Diazepam PO (5 to 10 mg/day in 2 divided doses) may be given for the first two weeks of treatment. During the first month, the patient should be followed weekly. During this period, do not give more tablets than the quantity required for each week. All serious depression carries the risk for suicide. Talking to patients about this will not increase the risk of suicide attempt. On the contrary depressed people are often anxious and ambivalent about suicide and feel relieved when able to talk about it.
298
If major symptoms have not resolved at all after a month at a normally-effective dose, refer the patient to a psychiatrist, if possible; if not, try a different antidepressant2.
The treatment should always be stopped gradually (over a 2-week period for SRIs, and a 4-week period for tricyclics). Inform the patient about problems associated with abrupt treatment discontinuation (very common with paroxetine).
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2 In case of treatment failure with an SRI: if the patient is under paroxetine, reduce the dose over a two-week
period to avoid withdrawal symptoms, then wait 2 to 4 days before starting the tricyclic antidepressant. If the patient is under fluoxetine, stop fluoxetine (withdrawal symptoms are unlikely) and wait at least 10 to 14 days before starting the tricyclic antidepressant. 299
Psychotic disorders
Psychotic disorders
Psychoses are characterised by delusions. The patient is convinced of things that are not real, based on intuition, interpretation or hallucinations especially auditory ones. Delusions are often accompanied by behaviour disorders, for example agitation, prostration, mutism, opposition, and fleeing. Management includes psychosocial support and antipsychotic medication. Treatment efficacy and the prognosis depend in large part on the quality of the relationship established with the patient and his family. Keeping the patient at home with outpatient follow-up is preferred if the patient is not a danger to himself or others, and if the family is capable of managing the disorder.
The meaning of psychoses varies with the cultural context1. For example, psychotic disorders may be attributed to charms or to ancestor intervention. Therapeutic approach should take those beliefs into account. Patient are usually already under traditional treatments, this should not be seen as an obstacle to conventional medical treatment.
An acute psychotic episode can be a one-time occurrence, usually of sudden onset, or can occur repeatedly or may be the early phase of chronic psychosis. It can occur following a life event (e.g., loss, acute stress or trauma). In postpartum psychosis, the delusions centre on the mother-child relationship. Antipsychotic therapy is the same as that for chronic psychoses (risperidone or haloperidol, page 301) and should last at least 3 months. After 3 months, if the patient is stable, stop the treatment gradually over 4 weeks, monitoring for potential relapse.
Before prescribing antipsychotic medication, consider the possibility of an underlying organic cause (see Mental confusion, page 294) or use of toxic substances. For severe anxiety or agitation, an short-course anxiolytic or sedative treatment (see page 302) may be added to the antipsychotic treatment, at the beginning of treatment.
Chronic psychoses
The chronic psychoses (schizophrenia, paranoid psychosis, etc.) are defined by specific clinical characteristics and their long-term nature. In schizophrenia, delusions are accompanied by dissociation; the patient seems odd, his speech and thoughts are incoherent, his behaviour unpredictable and his emotional expression discordant. Such patients are often very anxious. Delusions of persecution are common.
1 Hence the importance of working with an informant (in the anthropological sense of the word) when dealing
300
The goal of the treatment is to reduce psychological suffering and disabling symptoms, particularly on the relational level. It offers real benefits, even if chronic symptoms persist (tendency toward social isolation, possible relapses and periods of increased behavioural problems, etc.). The treatment should last at least one year, with a gradual dose reduction. Low dose may be maintained for longer periods if necessary. Uncertainty about the possibility of follow-up at one year or beyond is no reason not to treat. However, it is better not to start pharmacological treatment for patients who have no family/social support (e.g., homeless), provided they do not have severe behavioural disorders.
Start treatment at a low dose: risperidone PO: 2 mg in 2 divided doses on D1, then 4 mg/day in 2 divided doses as of D2. If insufficient, increase to 6 mg/day (8 mg/day maximum). or haloperidol PO2: 5 mg/day in 2 divided doses; if insufficient, 10 mg/day in 2 divided doses. Not to exceed 20 mg/day.
Risperidone (mg/day)
Antipsychotic therapy
Haloperidol (mg/day)
D1 2 1
W1-W2 4 2
4 to 6 2 to 4
W3
4 to 6 2 to 4
M1
W1 5 2
W2 5 2
5 to 10 2 to 5
W3
5 to 15 2 to 10
M1
Can be used
Monitor the newborn for the first few Monitor the newborn for the first few days of life if the mother received days of life. high doses during the 3rd trimester.
Extrapyramidal effects, which are more common with haloperidol than with risperidone, can be counteracted by adding biperiden PO: 2 to 4 mg/day in 2 divided doses.
Psychoses (first acute episode or decompensation of a chronic psychosis) are much less common during pregnancy than postpartum. In the event of pregnancy in a woman taking antipsychotics, re-evaluate the need to continue the treatment. If treatment is still necessary, refer to the table above. Monitor the newborn for extrapyramidal symptoms during the first few days of life. For postpartum psychosis, if the woman is breastfeeding, risperidone should be preferred to haloperidol.
2 If available, haloperidol decanoate IM (long-acting form) can be used in the long-term treatment of psychoses in
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301
Psychotic disorders
For severe anxiety or agitation, the following can be added, for a short period, at the beginning of the antipsychotic treatment: An anxiolytic, if the patient is anxious: diazepam PO: 5 to 15 mg/day in 2 or 3 divided doses for a few days Only use the injectable form in severe anxiety (diazepam IM: 10 mg, to be repeated once after one or two hours, if necessary), then change to diazepam PO as above. Another, more sedating, antipsychotic if the patient is agitated: chlorpromazine PO: 75 to 150 mg/day in 3 divided doses for a few days For very severe agitation, violence or opposition: haloperidol IM: 5 mg + chlorpromazine IM: 25 mg, to be repeated once after one or two hours, if necessary. In such cases, continue with haloperidol PO rather than risperidone (and if necessary, continue chlorpromazine PO as above for a few days). Bipolar disorder is characterised by alternating manic and depressive episodes 3, generally separated by normal periods lasting several months or years.
Bipolar disorder
Manic episodes are characterised by elation, euphoria and hyperactivity accompanied by insomnia, grandiose ideas, and loss of social inhibitions (sexual, in particular). Depressive episodes are often severe, with significant risk of suicide.
Pharmacologically: Manic episodes are treated with risperidone PO: start at a low dose of 2 mg once daily; increase if necessary in steps of 1 mg/day (maximum dose 6 mg/day) for 3 to 6 weeks. The medication should be stopped gradually, monitoring for possible relapse. Depressive episodes are treated as depression (see page 297). The primary treatment for bipolar disorder is a long-term mood stabiliser (lithium or carbamazepine).
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CHAPTER 12
Other conditions
Hypertension Heart failure in adults Endemic goitre and iodine deficiency 305 309 312
12
Hypertension
Adult essential hypertension is defined as a systolic pressure greater than or equal to 160 mmHg and/or a diastolic pressure greater than or equal to 90 mmHg. The elevation must be constant: blood pressure must be measured twice at rest during three consecutive consultations over a period of three months. Hypertension is a risk factor for stroke (cerebrovascular accident or CVA), heart failure, renal failure and atherosclerosis. Hypertension in pregnancy is defined as a systolic pressure greater than or equal to 140 mmHg or a diastolic pressure greater than or equal to 90 mmHg (with the patient seated and at rest). It may be isolated or associated with proteinuria or oedema in the case of pre-eclampsia. Hypertension in pregnancy is a risk factor for eclampsia, placental abruption and premature delivery.
In patients with medication-induced hypertension (oral contraceptives, hydrocortisone, MAO inhibitors, NSAID etc.), stop or change the treatment. Otherwise, start with diet and exercise modification: reduce salt intake, lose any excess weight, and increase the level of physical activity. If despite these measures the blood pressure remains consistently above 160/100 mmHg (or 140/80 mmHg for a diabetic patient or following a CVA), an antihypertensive medication may be added. Start with monotherapy. The optimal dose depends on the patient; reduce by half the initial dose for elderly patients. The three classes of anti-hypertensives used as initial therapy 1 are the thiazide diuretics, the beta-blockers and the angiotensin converting enzyme (ACE) inhibitors. For information:
Uncomplicated hypertension Patient over 65 years Diabetic patient Following a CVA Heart failure Renal failure Complicated hypertension:
Indications
thiazide diuretic or beta-blocker thiazide diuretic thiazide diuretic ACE inhibitor ACE inhibitor beta-blocker ACE inhibitor or beta-blocker
Initial treatment
1 The diuretics, beta-blockers, and ACE inhibitors have shown their capacity to prevent the complications of 2 Furthermore, a sudden stop to treatment with centrally acting anti-hypertensives (e.g. methyldopa, clonidine)
The treatment must be taken regularly. Abrupt cessation of beta-blocker treatment may cause adverse effects (malaise, angina)2. Only prescribe a treatment if it can be followed by a patient under regular surveillance.
hypertension. They are preferred to other anti-hypertensives, notably calcium channel blockers (nifedipine). may cause a rebound effect.
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305
Hypertension
Note: if enalapril3 is used as monotherapy (see table of indications), start with 5 mg once daily, then increase the dose every 1 to 2 weeks, according to blood pressure, up to 10 to 40 mg once daily or in 2 divided doses. In elderly patients, patients taking a diuretic or patients with renal impairment: start with 2.5 mg once daily as there is a risk of hypotension and/or acute renal impairment. Specific case: treatment of hypertensive crisis An occasional rise in blood pressure usually passes without problems, whereas aggressive treatment, notably with sublingual nifedipine, can have serious consequences (syncope, or myocardial, cerebral, or renal ischaemia). In patients with hypertensive crisis: Reassure the patient and place him at rest. If despite these measures the blood pressure remains elevated, the addition of furosemide PO (20 mg once daily) may, in certain cases, gradually reduce the blood pressure in 24 to 48 hours and prevent eventual complications. In patients with hypertensive crisis complicated by acute pulmonary oedema: The objective is not to normalise the blood pressure at any price, but to treat the pulmonary oedema (see page 308). Start or adjust the baseline treatment once the crisis is resolved.
The objective is to reduce the blood pressure to below 160/90 mmHg (or 140/90 mmHg for diabetic patients) while producing the fewest possible adverse effects. For uncomplicated hypertension: Start with a thiazide diuretic: hydrochlorothiazide PO 25 to 50 mg once daily. If the patient is not improving after 4 weeks, or if treatment is not tolerated: check compliance, and then if there are no contra-indications (asthma, uncontrolled heart failure), change to a beta-blocker: atenolol PO 50 to 100 mg once daily. If the treatment is still of little or no benefit: recheck compliance, and then consider combined therapy (thiazide diuretic + beta-blocker or thiazide diuretic + ACE inhibitor).
doses).
306
For severe pre-eclampsia (hypertension + massive proteinuria + major oedema) While waiting for delivery, observation, normal sodium and caloric intake.
hydralazine by
Rest and observation, normal sodium and caloric intake. Antihypertensive treatment if the systolic BP is 160 mmHg or the diastolic BP is 110 mmHg, as above. After 37 weeks, if there is a true intrauterine growth retardation: delivery, vaginally or by caesarean section depending on the cervical assessment. If there is no clear growth retardation, induce delivery as soon as the cervix is favourable. Refer to a surgical centre for urgent delivery within 24 hours, vaginally or by caesarean section depending on the cervical assessment and the foetus condition.
Antihypertensive treatment if the systolic BP is 160 mmHg or the diastolic BP is 110 mmHg, as above. If the treatment cannot be administered by oral route, use:
or hydralazine by slow, diluted IV injection: Dilute 20 mg (1 vial hydralazine, 1 ml) in 9 ml of 0.9% sodium chloride to obtain a solution containing 2 mg/ml. Administer 5 mg (2.5 ml of the diluted solution) over 2 to 4 minutes. Check BP for 20 minutes. If BP is not controlled after 20 minutes, administer the same dose. Continue repeating if necessary, waiting 20 minutes between each injection, without exceeding a cumulative dose of 20 mg. or labetalol (100 mg in 20 ml ampoule, 5 mg/ml) slow IV: One dose of 20 mg (4 ml) over at least one minute. Check BP 5 and 10 minutes after injection. If BP is not controlled, administer another dose of 20 mg and check BP. Additional doses of 40 mg, then 80 mg then 160 mg may be administered every 10 minutes until BP is controlled. Do not exceed a cumulative dose of 300 mg. Do not exceed recommended doses and administration rate. During administration, monitor maternal BP and pulse, as well as foetal heart rate. An overdose or too rapid administration may provoke an abrupt fall in maternal BP with placental hypoperfusion and foetal death. Diastolic BP must never fall below 90 mmHg. In the event of hypotension, use Ringer Lactate to maintain the diastolic BP 90 mmHg.
IV infusion: Dilute 100 mg (5 vials of hydralazine, 5 ml) in 500 ml of 0.9% sodium chloride or Ringer lactate, to obtain a solution containing 200 micrograms/ml. Initial dose: 200 to 300 micrograms/minute; maintenance dose: 50 to 150 micrograms/minute. Administer by increasing the rate up to 20 drops/minute (max. 30 drops/minute), check BP every 5 minutes. As soon as hypertension is controlled, decrease progressively the rate (15 drops/ minute, then 10, then 5) until stopping infusion. An abrupt discontinuation may provoke a hypertensive crisis.
To reduce the risk of eclampsia prior to delivery: magnesium sulfate: see page 25. Continue for 24 hours following delivery.
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307
Hypertension
For eclampsia
Urgent delivery within 12 hours, vaginally or by caesarean section depending on the cervical assessment and the foetus condition. Antihypertensive treatment if the systolic BP is 160 mmHg or the diastolic BP is 110 mmHg, as above. magnesium sulfate : see page 25. Continue for 24 hours following delivery or following the last seizure.
Nursing, hydration, monitor urinary output (insert a urinary catheter); oxygen (4 to 6 litres/minute). For more information, refer to the MSF handbook, Obstetrics.
308
Clinical features
Left-sided heart failure secondary to left ventricular failure: fatigue and/or progressive dyspnoea, occurs on exertion and then at rest (accentuated by the decubitus position, preventing the patient from lying down) acute pulmonary oedema: acute dyspnoea, laryngeal crackles, cough, frothy sputum, anxiety, pallor, varied degrees of cyanosis, feeble rapid pulse, wet rales in both lung fields, muffled heart sounds, often with cardiac gallop Right-sided heart failure secondary to right ventricular failure: oedema of the lower limbs, jugular venous distention, hepatomegaly, hepatojugular reflux ascites in advanced stages Rarely isolated, this is often a consequence of left ventricular failure. Global heart failure secondary to failure of both ventricles: left and right-sided signs. Signs of right ventricular failure are often the most prominent.
Treatment of acute heart failure (acute pulmonary oedema and cardiogenic shock)
First case: blood pressure is maintained Place the patient in the semi-reclined position with legs lowered. Give high-flow oxygen Reduce pulmonary pressure with combination furosemide + morphine + rapidlyacting nitrate derivatives: furosemide IV (onset of action in 5 minutes and peak effect in 30 minutes): 40 to 80 mg/injection, to be repeated every 2 hours according to clinical evolution. Monitor blood pressure and urine output. + morphine: according to severity 3 to 5 mg by slow IV injection or 5 to 10 mg by SC injection + glyceryl trinitrate sublingual: 0.25 to 0.5 mg. Monitor blood pressure. Repeat after 30 minutes if necessary, only if the systolic blood pressure remains above 100 mmHg. In certain serious cases, if none of these drugs are available, bleed off 300 to 500 ml of blood over 5 to 10 minutes from the basilic vein (in the elbow fold) and monitor the blood pressure.
Second case: blood pressure collapsed, see cardiogenic shock, page 21.
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309
The objective is to improve the prognosis and quality of life. Treatment of fluid retention
Dietary modification: reduce salt intake to limit fluid retention, normal fluid intake (except in the case of anasarca: 750 ml/24 hours). Initial therapy: furosemide PO During congestive episodes: 40 to 120 mg once daily. When the congestive episode is controlled, reduce the dose to 20 mg once daily. The dose can be increased (up to 240 mg/day). If these doses are still ineffective, adding hydrochlorothiazide PO (25 to 50 mg/day for several days) may be considered. In case of treatment failure and in the absence of severe renal impairment, furosemide may be combined with spironolactone PO: 25 mg once daily. If present, drainage of pleural effusions by needle aspiration. Note: the risks of administering diuretics include: dehydration, hypotension, hypo- or hyperkalaemia, hyponatremia, and renal impairment. Clinical monitoring (hydration, blood pressure) and if possible metabolic monitoring (serum electrolytes and creatinine), should be done regularly, especially if giving high doses or in elderly patients. Angiotensin converting enzyme (ACE) inhibitors are the first line treatment. Start with low doses, especially in patients with low blood pressure, renal impairment, hyponatremia, or concurrent diuretic treatment. enalapril PO1: 5 mg once daily for the first week, then double the dose each week until the effective dose is reached, usually around 10 to 40 mg once daily or in 2 divided doses. Increases in the dose are made while monitoring the patient's blood pressure (the systolic pressure should remain above 90 mmHg) and blood chemistry (there is a risk of hyperkalemia2 and renal impairment). In patients treated with diuretics, reduce the dose of the diuretic if possible while introducing ACE inhibitors. If the patient is taking high doses of diuretics, reduce the initial dose of enalapril to half (risk of symptomatic hypotension). Do not combine ACE inhibitors and spironolactone (risk of severe hyperkalemia).
Baseline treatment
Digitalis glycosides are only indicated in patients with proven atrial fibrillation (ECG). If there are no contra-indications (bradycardia, unidentified rhythm disturbances): digoxine PO: 0.5 to 1 mg in 3 or 4 divided doses on the first day, then 0.25 mg once daily The therapeutic dose is close to the toxic dose. Do not exceed the indicated dose and give half the dose, or even a quarter (on alternate days) to elderly or malnourished patients and to patients with renal impairment.
1 Enalapril may be replaced by captopril: start with 6.25 mg three times daily for the first week, the effective dose
is usually around 50 mg twice daily. The method of increasing the dose, the precautions, and patient monitoring are the same as for enalapril. 2 Moderate hyperkalaemia is frequent, but of no concern if it remains below 5.5 mEq/l. 310
With global and left-sided heart failure, the nitrate derivatives may be used in case of signs of intolerance to ACE inhibitors (chronic cough, renal impairment, severe hypotension). isosorbide dinitrate PO: start with 10 to 15 mg/day in 2 or 3 divided doses and increase to the effective dose, usually around 15 to 60 mg/day. Very high doses (up to 240 mg/day) may be necessary. Whatever the treatment prescribed, monitoring should be regular: checking clinical improvement and treatment tolerance: - clinical monitoring consists of evaluating the weight, blood pressure, pulse (rhythm disturbances) and the progress of signs (dyspnoea, oedema, etc.); - laboratory monitoring is adapted according to the treatment.
Hypertension (see page 305); anaemia (see page 37) or IV Children: 25 to 50 mg/day for several days Adults: 50 to 100 mg/day for several days Then change to oral treatment with thiamine PO Children and adults: 3 to 5 mg once daily for 4 to 6 weeks Acute rheumatic fever Antibiotic treatment
benzathine benzylpnicillin IM
Anti-inflammatory treatment Start with acetylsalicylic acid PO: 50 to 100 mg/kg/day If the fever or cardiac signs persist, replace with a corticosteroid: prednisolone PO Children: 1 to 2 mg/kg/day Adults: 60 to 120 mg/day Continue this treatment for 2 to 3 weeks after normalisation of the erythrocyte sedimentation rate (ESR), then decrease the doses progressively (over 2 weeks). To avoid a relapse, resume the acetylsalicylic acid treatment in parallel with the decrease in prednisolone dose. The acetylsalicylic acid treatment is continued for 2 to 3 weeks after the corticosteroids are fully stopped. Secondary prophylaxis Prophylactic treatment lasts for several years (until 18 years old, even until 25 years in the case of cardiac effects; for life in the case of chronic valvular damage). benzathine benzylpenicillin IM Children under 30 kg: 600 000 IU as a single dose every 4 weeks Children over 30 kg and adults: 1.2 MIU as a single dose every 4 weeks
311
Children under 30 kg: 600 000 IU as a single dose Children over 30 kg and adults: 1.2 MIU as a single dose
12
Clinical features
The WHO proposes a simplified classification based on the significance of goitre: Group 0: normal thyroid, no palpable or visible goitre Group 1: enlarged thyroid, palpable but not visible when the neck is in the normal position Group 2: thyroid clearly visible when the neck is in the normal position Possible mechanical complications (rare): compression, deviation of the trachea or of the oesophagus. The objective of prevention is to reduce the consequences of iodine deficiency in neonates and children. Supplying iodised salt through national programmes is the recommended method of prevention. For prevention in populations living in iodine deficient areas where iodised salt is not available and for curative treatment of patients with goitre: use iodised oil, according to national protocols. For information (according to the WHO):
Population Oral iodised oil as a single yearly dose (200 mg capsule) 2 capsules 3 capsules 1 capsule IM iodised oil, every 2 years using a glass syringe (480 mg/ml ampoule) 240 mg (0.5 ml) 480 mg (1ml) 480 mg (1ml) 480 mg (1ml)
Curative and preventive single-doses are the same. Oral treatment is preferred. Use injectable iodised oil for prevention only if annual administration of oral iodised oil is not possible. The target populations are pregnant and breastfeeding women, women of childbearing age and children. In children, goitre disappears after several months. It disappears more slowly (or never) in adults despite restoration of normal thyroid function in 2 weeks. Surgery is only indicated for patients with local mechanical dysfunction.
312
2 capsules
Annexes
The interagency emergency health kit Annex 2 (WHO) Practical advice for writing medical certificates in the event of sexual violence List of the drugs mentioned in this guide, including the International Nonproprietary Names (INN) Main references Index 315 322 325 328 330
A
1. Look at: Conditiona Eyesb Thirst Well, alert Normal Drinks normally, not thirsty
B
Restless, irritable Sunken Thirsty, drinks eagerly
C
Lethargic or unconscious Sunken Drinks poorly or not able to drink
Goes back quickly The patient has no signs of dehydration Use Treatment Plan A
Goes back slowly If the patient has two or more signs in B, there is some dehydration Weigh the patient, if possible, and use Treatment Plan B
Goes back very slowly If the patient has two or more signs in C, there is severe dehydration Weigh the patient and use Treatment Plan C Urgently
4. Treat:
Being lethargic and sleepy are not the same. A lethargic child is not simply asleep: the child's mental state is dull and the child cannot be fully awakened; the child may appear to be drifting into unconsciousness. b In some infants and children the eyes normally appear somewhat sunken. It is helpful to ask the mother if the childs eyes are normal or more sunken than usual. c The skin pinch is less useful in infants or children with marasmus or kwashiorkor or in obese children.
53
Department of Child and Adolescent Health and Development. The treatment of diarrhoea - a manual for physicians and other senior health workers. Geneva: World Health Organization; 2005.
315
A-2.2
preventdehydrationathomebygivingthechildmorefluidthanusual; prevent malnutrition by continuing to feed the child, and why these actions are important; recognizesignsindicatingthatthechildshouldbetakentoahealthworker.
ThefourrulesofTreatmentPlanA: Rule 1: Give the child more fluids than usual, to prevent dehydration
Use recommended home fluids. These include: ORS solution, salted drinks (e.g. salted ricewaterorasaltedyogurtdrink),vegetableorchickensoupwithsalt. Avoid fluids that do not contain salt, such as: plain water, water in which a cereal has been cooked (e.g. unsalted rice water), unsalted soup, yoghurt drinks without salt, green coconut water, weak tea (unsweetened), unsweetened fresh fruit juice. Other fluids to avoid are those with stimulant, diuretic or purgative effects, for example: coffee,somemedicinalteasorinfusions. Be aware of fluids that are potentially dangerous and should be avoided during diarrhoea. Especially important are drinks sweetened with sugar, which can cause osmotic diarrhoea and hypernatraemia. Some examples are: commercial carbonated beverages,commercialfruitjuices,sweetenedtea. UseORSsolutionforchildrenasdescribedintheboxbelow.(Note:ifthechildisunder 6monthsandnotyettakingsolidfood,giveORSsolutionorwater.)
Give as much as the child or adult wants until diarrhoea stops. Use the amounts shown below for ORS as a guide. Describe and show the amount to be given after each stool is passed,usingalocalmeasure.
Age 24 months 2 - 10 years 10 years Amount of ORS to be given after each loose stool 50-100 ml 100-200 ml as much as wanted Amount of ORS to provide for use at home 500 ml/day 1L/day 2L/day
ShowthemotherhowtomixORSandshowherhowtogiveORS.
Giveateaspoonfulevery12minutesforachildunder2years. Givefrequentsipsfromacupforolderchildren.
316
Ifthechildvomits,wait10minutes.Thengivethesolutionmoreslowly(forexample,a spoonfulevery23minutes). If diarrhoea continues after the ORS packets are used up, tell the mother to give other fluidsasdescribedinthefirstruleaboveorreturnformoreORS.
Rule 2: Give supplemental zinc sulfate 20 mg tab to the child, every day for 10 to 14 days Zinc sulfate can be given as dispersible tablets. By giving zinc sulfate as soon as diarrhoea starts, the duration and severity of the episode as well as the risk of dehydration will be reduced. By continuing zinc sulfate supplementation for 10 to 14 days, the zinc lost during diarrhoea is fully replaced and the risk of the child having new episodes of diarrhoea in the following2to3monthsisreduced. Rule 3: Continue to feed the child, to prevent malnutrition
Breastfeedingshouldalwaysbecontinued. Theinfantsusualdietshouldbecontinuedduringdiarrhoeaandincreasedafterwards; Foodshouldneverbewithheldandthechildsusualfoodshouldnotbediluted; Most children with watery diarrhoea regain their appetite after dehydration is corrected; Milk: Infantsofanyagewhoarebreastfedshouldbeallowedtobreastfeedasoftenand aslongastheywant.Infantswilloftenbreastfeedmorethanusual,encouragethis; Infants who are not breastfed, should be given their usual milk feed (formula) at leasteverythreehours,ifpossiblebycup. Infants below 6 months of age who take breast milk and other foods should receive increased breastfeeding. As the child recovers and the supply and the supplyofbreastmilkincreases,otherfoodsshouldbedecreased. A child who is at least 6 months old or is already taking soft foods should be given cereals, vegetables and other foods, in addition to milk. If the child is over 6 months and such foods are not yetbeing given, they should be started during the diarrhoeaepisodeorsoonafteritstops. Recommended food should be culturally acceptable, readily available. Milk should be mixed with a cereal and if possible, 1 2 teaspoonfuls of vegetable oil should be addedtoeachservingofcereal.Ifavailable,meat,fishoreggshouldbegiven. Foodsrichinpotassium,suchasbananas,greencoconutwaterandfreshfruitjuice arebeneficial; offerthechildfoodeverythreeorfourhours(sixtimesaday); after the diarrhoea stops, continue to give the same energyrich food, and giveonemoremealthanusualeachdayforatleasttwoweeks.
317
Rule 4: Take the child to a health worker if there are signs of dehydration or other problems Themothershouldtakeherchildtoahealthworkerifthechild:
Treatment Plan B: oral rehydration therapy for children with some dehydration
Table 2: Guidelines for treating children and adults with some dehydration
Approximate amount of ORS solution to give in the first 4 hours Age* Weight Quantity In local measure Use the patient's age only when you do not know the weight. The approximate amount of ORS required (in ml) can also be calculated by multiplying the patients weight in kg by 75. If the patient wants more ORS than shown, give more. Encourage the mother to continue breastfeeding her child. <4 mths < 5 kg 200-400 ml 4-11 mths 5-7.9 kg 400-600 ml 12-23mths 8-10.9 kg 600-800 ml 2-4 years 11-15.9 kg 800 ml-1.2 L 5-14 years 16-29.9 kg 1.2-2 L 15 years 30 kg 2.2-4 L
NOTE: during the initial stages of therapy, while still dehydrated, adults can consume up to 750 ml per hour, if necessary, and children up to 20 ml per kg body weight per hour.
TeachafamilymembertoprepareandgiveORSsolution. Use a clean spoon or cup to give ORS solution to infants and young children. Feeding bottlesshouldnotbeused. UsedroppersorsyringestoputsmallamountsofORSsolutionintomouthsofbabies. Children under 2 years of age, should get a teaspoonful every 12 minutes; older children(andadults)maytakefrequentsipsdirectlyfromacup. Checkfromtimetotimetoseeifthereareproblems. If the child vomits, wait 510 minutes and then start giving ORS again, but more slowly,forexample,aspoonfulevery23minutes.
318
If the childs eyelids become puffy, stop the ORS and give plain water or breast milk. GiveORSaccordingtoPlanAwhenthepuffinessisgone.
Checkthechildfrequentlyduringrehydration. Ensure that ORS solution is being taken satisfactorily and the signs of dehydration are notworsening. Afterfourhours,reassessthechildfullyfollowingtheguidelinesinTable1anddecide whattreatmenttogive. Ifsignsofseveredehydrationhaveappeared,shifttoTreatmentPlanC. If signs indicating some dehydration are still present, repeat Treatment Plan B. At the same time offer food, milk and other fluids as described in Treatment Plan A, and continuetoreassessthechildfrequently. If there are no signs of dehydration, the child should be considered fully rehydrated. Whenrehydrationiscomplete: skinpinchisnormal; thirsthassubsided; urineispassed; childbecomesquiet,isnolongerirritableandoftenfallsasleep. TeachthemotherhowtotreatherchildathomewithORSsolutionandfoodfollowing TreatmentPlanA.GiveherenoughORSpacketsfor2days. Also teach her the signs that mean she should bring her child back to see a health worker.
Ifsignsofdehydrationpersistorreappear,referthechild.
Begin to give supplemental zinc sulfate tablets, as in Treatment Plan A, as soon as the childisabletoeatfollowingtheinitialfourhourrehydrationperiod.
Giving food
Except for breast milk, food should not be given during the initial fourhour rehydrationperiod.
319
Children continued on Treatment Plan B longer than four hours should be given some foodevery34hoursasdescribedinTreatmentPlanA. All children older than 6 months should be given some food before being sent home. This helps to emphasize to mothers the importance of continued feeding during diarrhoea.
320
Yes
Start IV fluids immediately. If the patient can drink, give ORS by mouth while the drip is set up. Give 100 ml/kg Ringers Lactate Solution (or if not available normal saline), divided as follows:
Age Infants (under 12 months) Older First give 30 ml/kg in: 1 hour* 30 minutes* Then give 70 ml/kg in: 5 hours 2 hours
No
Reassess the patient every 1-2 hours. If hydration is not improving, give the IV drip more rapidly. Also give ORS (about 5 ml/kg/hour) as soon as the patient can drink: usually after 2-4 hours (infants) or 1-2 hours (older patients). After 6 hours (infants) or 3 hours (older patients), evaluate the patient using the assessment chart. Then choose the appropriate Plan (A, B or C) to continue treatment. Send the patient immediately for IV treatment. If the patient can drink, provide the mother with ORS solution and show her how to give it during the trip to receive IV treatment.
Yes
No
Yes
Start rehydration by tube with ORS solution: give 20 ml/kg/hour for 6 hours (total of 120 ml/kg).
if there is repeated vomiting or increased abdominal distension, give the fluid more slowly. if hydration is not improved after 3 hours, send the patient for IV therapy.
No
Yes
After 6 hours, reassess the patient and choose the appropriate treatment plan. Start rehydration by mouth with ORS solution, giving 20 ml/kg/hour for 6 hours (total of 120 ml/kg).
if there is repeated vomiting, give the fluid more slowly - if hydration is not improved after 3 hours send the patient for IV therapy.
No
After 6 hours, reassess the patient and choose the appropriate treatment plan.
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Practical advice for writing medical certificates in the event of sexual violence
Faced with sexual violence, the physician is obliged to complete a medical certificate for the benefit of the victim, irrespective of the country in which (s)he is practising. The certificate is individual (for the benefit of the individual or their beneficiaries) and confidential (it falls within professional confidentiality). The examples of certificates presented in the following pages are written for sexual violence, but the approach is the same for all forms of intentional violence. All medical certificates must include: The identity of the signing physician. The identity of the victim (except for certificates passed on to HCR or to ICRC without the consent of the victim, see below). The complete date and the time of the examination. The statement of the victim in his/her own words. The findings of the clinical examination. The samples taken and the examinations carried out. A conclusion (including, if possible, the length of Total Temporary Incapacity (TTI) and anticipated Partial Permanent Incapacity (PPI)). Notes: The name of the victim (except for certificates passed on to HCR or to ICRC without the consent of the victim, see below), the name of the physician and his/her signature, as well as the date of the examination must appear on each page. A copy containing the victims name is given to the victim for future legal use. Keep a copy of the medical certificate (or, if the case should arise, of the mandatory report1) in the patient record, archived to allow future authentication of the certificate given to the victim.
Physicians are often the first to be confronted with the consequences of violence. Victims are sometimes afraid to report to the authorities concerned, particularly when the population affected is vulnerable (refugees, prisoners, civilian victims of war etc.). In such a situation, the physician should try to determine if the event was isolated or part of larger scale violence (e.g. systematic rape).
With the consent of the victim, the physician gives a copy of the certificate containing the victims name: to HCR (to the protection officer only) if the victim is a refugee or displaced, so that protection measures may be put in place for the individual; to ICRC if the victim is a victim of war or a prisoner. Without the consent of the victim, the physician may give a copy of the certificate to HCR or ICRC, but without revealing the identity of the victim (concretely, the sections family name, first name and precise address should not appear).
1 In principle, legal reporting of sexual violence against children under 15 years is mandatory. The only exception
What the practitioner should not do: Rephrase the words of the victim as the practitioners own. Endorse the identity of the aggressor nor the nature of the crime, this must be left to the legal authorities. Conclude that there was no sexual violence in the absence of lesions on clinical examination. Examples of medical certificates for adults and children (see following pages).
is if there is a risk that reporting may further harm the situation of the child. Consider each case individually.
322
Practical advice for writing medical certificates in the event of sexual violence
On somatic examination: ..................................................................................................................... (describe precisely all lesions observed on the entire body: signs of abrasion, cuts, scratches, bites, strangulation, swelling, burns etc. Indicate the site, the extent, the number, the character (old or recent), the severity etc.) On genital examination: ....................................................................................................................... (is the hymen intact or not (if not, did it occur recently or in the past), traumatic lesions etc.) Examinations completed (particularly samples taken): .................................................................. Evaluate the risk of pregnancy: .......................................................................................................... On anal examination: ............................................................................................................................ (detectable traumatic lesions etc.)
Total Temporary Incapacity (TTI) should be granted for .......... days without consideration of possible complications. Sequelae may persist leaving a Partial Permanent Incapacity (PPI) to be assessed by an expert at a future date. This document is established with the consent of the patient and may be used for legal purpose. Signature of physician
In conclusion, Mr, Mrs, Miss ................................................. shows (or does not show) signs of recent violence and an emotional response (in)compatible with the violence of which (s)he reports to have been victim. (Remember: the absence of lesions does not allow a conclusion that there was no sexual violence).
323
Practical advice for writing medical certificates in the event of sexual violence
On somatic examination: ...................................................................................................................... (describe precisely all lesions observed on the entire body: signs of abrasion, cuts, scratches, bites, strangulation, swelling, burns etc. Indicate the site, the extent, the number, the character (old or recent), the severity etc.) On genital examination: ....................................................................................................................... (is the hymen intact or not (if not, did it occur recently or in the past), traumatic lesions, genital infection etc.) On anal examination: ........................................................................................................................... (detectable traumatic lesions etc.)
Examinations completed (particularly samples taken): .................................................................. Evaluate the risk of pregnancy: ..........................................................................................................
Total Temporary Incapacity (TTI) should be granted for .......... days without consideration of possible complications. Sequelae may persist leaving a Partial Permanent Incapacity (PPI) to be assessed by an expert at a future date. This document is established with the consent of ............................................. (father, mother or legal representative) and may be used for legal purpose. Signature of physician
324
In conclusion, this child shows (or does not show) signs of recent violence and an emotional response (in)compatible with the violence of which (s)he reports to have been victim. (Remember: the absence of lesions does not allow a conclusion that there was no sexual violence).
List of the drugs mentioned in this guide, including the International Nonproprietary Names (INN)
as well as the most common synonyms and proprietary names
Abacavir = ABC: Abac, Abamune, Ziagen Aciclovir: Viratup, Zovirax Acetylsalicylic acid = ASA = Aspirin Albendazole : Eskazole, Zentel Aluminium hydroxide: Maalox Amoxicillin: Amoxil, Clamoxyl Amphotericin B: Fungizone Ampicillin: Pentrexyl Artemether: Paluther Amitriptyline: Elavil, Laroxyl, Triptyzol Amodiaquine: Camoquine, Flavoquine Amoxicillin/clavulanic acid = co-amoxiclav: Augmentin Amphotericin B liposomal: AmBisome Artemether/lumefantrine = co-artemether: Coartem, Riamet Artesunate: Arsumax, Plasmotrim Artesunate/amodiaquine: Coarsucam Atenolol: Tenormin Ascorbic acid = vitamin C: Laroscorbine, Vitascorbol Azithromycin: Zithromax Beclometasone: Beclazone, Becotide
Benzyl benzoate: Ascabiol Biperiden: Akineton Bisacodyl: Dulcolax Bithionol: Bitin Calcium gluconate
Carbamazepine: Tegretal, Tegretol Cefazolin: Cefacidal, Kefzol Cefotaxime : Claforan Ceftriaxone: Rocephin
Chloramphenicol: Chloromycetin, Kemicetine Chloramphenicol (long-acting oily) Chloroquine: Nivaquine Chlorphenamine = chlorpheniramine: Teldrin, Trimeton Chlorpromazine: Largactil, Megaphen, Thorazine Cimetidine: Tagamet Ciprofloxacin: Ciflox Clindamycin: Dalacin
Clofazimine: Lamprene
Clomipramine: Anafranil
Benzylpenicillin procaine = penicillin G procaine: Depocillin, Duracillin Benzylpenicillin procaine + benzylpenicillin = Fortified penicillin procaine: Bicillin Benznidazole: Radanil
Co-amoxiclav = amoxicilline/acide clavulanique: Augmentin Co-artemether = artmther/lumefantrine: Coartem, Riamet Codeine Co-trimoxazole = sulfamethoxazole + trimethoprim: Bactrim Dapsone: Avlosulfon, Disulone 325
Diazepam: Valium
Diclofenac: Cataflam, Voltaren Didanosine = ddI = Videx Diethylcarbamazine: Banacide, Hetrazan, Notezine Digoxin: Coragoxine, Lanoxin Dopamine: Dynatra, Intropin Doxycycline: Vibramycin Eflornithine: Ornidyl Enalapril: Renitec Efavirenz: Stocrin, Sustiva Epinephrine = adrenaline Diphtheria-Tetanus-Pertussis vaccine
Isoniazid = INH: Cemidon, Rimifon Ivermectin: Mectizan, Stromectol Ketamine: Ketalar, Ketanest Ketoconazole cream: Nizoral Lactulose: Duphalac Japonese Encephalitis vaccine: JE-Vax
Lamivudine = 3TC: Epivir, Lamivir Lidocaine = Lignocaine: Xylocaine Loperamide: Imodium, Imosec Magnesium sulphate Measles vaccine: Malathion: Prioderm
Ergocalciferol = vitamin D2
Erythromycin: Erythrocin, Pantomicina, Propiocine Ethambutol: Dexambutol, Myambutol Ferrous salts (sulphate or fumarate) Fluconazole: Triflucan Folic acid = vitamin B9 Fluoxetine: Fluctine, Prozac Folinic acid: Refolinon Furosemide = frusemide: Lasilix, Lasix, Seguril Gentamicin: Genticin Gentian violet = crystal violet = GV Glucose 10% = dextrose 10% Glucose 50% = dextrose 50% Glyceryl trinitrate = nitroglycerin = trinitrin Haloperidol: Haldol, Serenace Hepatitis B vaccine Hydralazine: Apresoline
Mebendazole: Pantelmin, Vermox, Wormin Mefloquine: Lariam Meglumine antimoniate: Glucantime Melarsoprol: Arsobal Meningococcal A+C vaccine Metronidazole: Flagyl Minocycline: Minocin Misoprostol Morphine Meningococcal A+C+W135 vaccine Metoclopramide: Primperan Miconazole muco-adhesive: Tibozole Modified fluid gelatin: Gelofusine, Plasmion Morphine (immediate-release): Sevredol Morphine (sustained-release): Kapanol Naloxone: Nalone, Narcan Nelfinavir: Viracept
Hydrochlorothiazide: Esidrex, HydroSaluric Hydrocortisone: Efcortesol, Cortagen, Solucortef Hyoscine butylbromide = butylscopolamine: Buscopan Ibuprofen: Advil, Brufen, Nureflex 326
Nevirapine: Neravir, Nevimune, Viramune Niclosamide: Tredemine, Yomesan Nifedipine: Adalat Nicotinamide = vitamin PP = vitamin B3: Nicobion Nifurtimox: Lampit Nitrofurantoine: Furadantin
List of the drugs mentioned in this guide Nystatine: Mycostatine, Nystan Omeprazole: Mopral Oral rehydration salts = ORS Oxytocin: Syntocinon Paracetamol = acetaminophen: Doliprane, Panadol Paromomycin = aminosidin: Humatin, Gabbroral Pentamidine: Pentacarinat, Pentam Permethrin 1% = Lyclear Phenobarbital: Gardenal, Luminal Permethrin 5%: Lyclear dermal cream Phenoxymethylpenicillin = penicillin V: Oracillin, Ospen Phenytoin: Di-hydran, Dilantin, Epanutin Phytomenadione = vitamin K1 Poliomyelitis vaccine (oral) Polygeline: Haemaccel Podophyllotoxin: Condyline, Condylox, Wartec Polyvidone iodine = povidone iodine: Betadine Potassium chloride: Kaleorid Praziquantel: Biltricide, Cysticide Promethazine: Phenergan Pyrazinamide: Zinamide Quinine Prednisone and prednisolone: Cortancyl, Solupred Pyridoxine = vitamin B6: Hexobion, Pyroxin Pyrimethamine: Daraprim, Malocide Rabies immunoglobulin Rabies vaccine: ReSoMal = ORS formula for severly malnourished children Retinol = vitamin A Ribavirine: Rebetol, Virazole Rifampicin: Rifadin Ritonavir: Norvir Ringer lactate = Hartmanns solution Salbutamol = albuterol: Salbulin, Ventolin Saquinavir: Invirase, Fortovase Silver sulfadiazine: Flamazine
Sodium valproate: = valproic acid: Convulex, Depakine, Epilim Spironolactone: Aldactone, Spiroctan Sulfadiazine: Adiazine Suramin: Germanin Tetanus vaccine Stavudine = d4T: Stavir, Zerit, Zeritavir Sulfadoxine/pyrimethamine: Fansidar Tenofovir = TDF: Viread Tetanus immunoglobulin Tetracycline eye ointment Tinidazole = Fasigyn
Thiamine = vitamin B1: Benerva, Betaxin Tramadol: Tramal, Zamadol, Zydol Triclabendazole: Egaten, Fasinex Vitamin A = retinol Valproic acid = sodium valproate: Convulex, Depakine, Epilim Whitfield ointment or benzoic acid 6% + salicylic acid 3% ointment Yellow Fever vaccine Zinc sulfate Zidovudine: Retrovir
327
Main references
Main references
WHO Publications
WHO. Symptom relief in terminal illness, Geneva, 1998. WHO. Management of severe malnutrition. A manual for physicians and other senior health workers, Geneva, 2000. WHO. The management of nutrition in major emergencies, Geneva, 2000. WHO. The clinical use of blood handbook, Geneva, 2001. WHO. Guidelines for the treatment of malaria, Geneva, 2006. WHO. Management of severe malaria. A practical handbook, Geneva, 2000. WHO in collaboration with MSF. Human African Trypanosomiasis. A guide for drug supply, Geneva, 2002. WHO. WHO Expert Committee on Rabies. Technical report series, 8th report, Geneva, 1992. WHO. Plague manual, Geneva, 1999. WHO/INAIDS. Safe and effective use of antiretroviral treatments in adults with particular reference to resource limited settings, Geneva, 2000. WHO. Guidelines for the management of sexually transmitted infections, Geneva, 2003.
WHO. Dengue haemorrhagic fever. Diagnosis, treatment, prevention and control, Geneva, 1997. WHO. Managing complications in pregnancy and childbirth. A guide for midwives and doctors, Geneva, 2003. WHO. Hospital care for children. Guidelines for the management of common illnesses with limited resources, 2005. WHO. WHO Model Formulary, Geneva, 2006.
Other publications
American Public Health Association. Control of communicable diseases manual, 2004. Harrisons Principles of Internal Medicine, 16th ed., McGraw-Hill Education, 2004.
328
British Medical Association and Pharmaceutical Society of Great Britain. British National Formulary, n 52, 2006.
Main references
Mansons tropical diseases, 21st ed., Gordon C Cook editor, 2002. The Sanford. Guide to HIV/AIDS therapy, 2005.
Oxford Medical Publications. Oxford handbook of tropical medicine, Oxford University Press, 2005. Transactions of Royal Society of Tropical Medicine and Hygiene. Leishmaniasis in Sudan, vol 95, 2001.
329
Index
Index
Abnormal vaginal discharge..........................233 Abortion............................................................247 Abortion, threatened .......................................247 Abruptio placenta............................................249 Abscess, acute dental ......................................287 Abscess, acute dento-alveolar........................287 Abscess, amoebic liver ......................................88 Abscess, breast .................................................276 Abscess, parotid...............................................278 Abscess, peritonsillar ........................................54 Abscesses ..........................................................274 Acute flaccid paralysis....................................193 Acute psychotic episode.................................300 Agitation ...........................................................293 AIDS ..................................................................207 Amoebiasis ....................................................83,88 Anaemia ..............................................................37 Ancylostomiasis...............................................154 Angiomatosis, bacillary ..................................217 Anthrax, cutaneous .........................................109 Anxiety..............................................................291 Ascariasis ..........................................................154 Asthma attack ....................................................74 Asthma, acute.....................................................74 Asthma, chronic .................................................76 Bejel....................................................................112 Beriberi ..............................................................310 Bipolar disorder ...............................................302 Bites, venomous ...............................................283 Borreliosis .........................................................182 Bronchiolitis........................................................64 Bronchitis, acute.................................................62 Bronchitis, chronic .............................................63 Brucellosis.........................................................176 Burns..................................................................266
Conjunctivitis ...................................................123 Conjunctivitis, neonatal..................................124 Cryptococcosis ..........................................215,218 Cryptosporidiosis .....................................147,213 Cyclosporiasis ..................................................147 Cysticercosis .....................................................153 Cystitis, acute ...................................................224 Dehydration, WHO protocol .........................315 Delirium trements ...........................................293 Dengue fever ....................................................201 Dental abscess, acute.......................................287 Dental infections ..............................................287 Dento-alveolar abscess, acute ........................287 Depression ........................................................297 Dermatitis, diaper............................................103 Dermatitis, seborrhoeic...................................217 Dermatology, examination ...............................97 Dermatophytoses.............................................104 Diarrhoea, acute.................................................83 Diarrhoea, parasitic .........................................147 Diphtheria...........................................................55 Diphyllobothriasis ...........................................152 Donovanosis.....................................................236 Dressings...........................................................253 Duodenum disorders ........................................89 Dysentery................................................86,88,213 Dyspepsia ...........................................................91 Eclampsia.....................................................25,307 Ectopic pregnancy ...........................................247 Eczema...............................................................117 Endometritis .....................................................240 Enterobiasis ......................................................155 Envenomation ..................................................283 Epiglottitis, acute ...............................................51 Epilepsy...............................................................24 Erysipela ...........................................................107 Fasciitis, necrotising ........................................108 Fever .............................................................26,220 Fever, relapsing ................................................182 Fever, yellow ....................................................204 Fevers, haemorrhagic viral.............................204 Filariasis ............................................................157 Filariasis, lymphatic ........................................161 Flukes ................................................................149 Folic acid deficiency ..........................................38 Fungal infections, superficial.........................103 Furuncle ............................................................106
Campylobacter ....................................................213 Candidiasis, intestinal................................92,214 Candidiasis, vaginal.................................233,244 Carbuncle..........................................................106 Cataract .............................................................128 Certificates, medical (sexual violence) .........322 Cervicitis ...........................................................233 Cestodes ............................................................152 Chagas disease ................................................142 Chancroid ..................................................236,245 Chlamydia ..........................................231,233,244 Cholera ................................................................84 Clinical examination .........................................10 Confusion (mental)..........................................294
330
Index
Gastrointestinal bleeding .................................90 Gastro-oesophageal reflux disease..................89 Genital infections......................................229,244 Genital ulcers ...................................................236 Giardiasis .....................................................83,147 Goitre, endemic................................................312 Gonorrhoea.........................................231,233,244 Haemolytic anaemia .........................................38 Haemorrhagic disease of the newborn, phytomenadione prophylaxis .................177 Haemorrhagic fevers, viral.............................204 Hansens disease ..............................................113 Headache and HIV ..........................................218 Heart failure in adults.....................................309 Hepatitis, viral..................................................198 Herpes simplex ................................................116 Herpes zoster....................................................116 Herpes, genital ..........................................236,245 Herpes, oral .................................................92,214 Hidradenitis, axillary ......................................217 Histoplasmosis.................................................215 History taking ....................................................10 HIV infection ....................................................207 Hookworm infection .......................................154 Hydatid cyst .....................................................153 Hymenolepiasis ...............................................152 Hypertension....................................................305 Hypoglycaemia..................................................24 Impetigo............................................................105 Infections extending into the cervicofacial tissues ...............................................288 Infections, genital .....................................229,244 Infections, upper genital tract........................240 Insomnia ...........................................................292 Iodine deficiency..............................................312 Iron deficiency....................................................38 Isosporiasis ................................................147,213 Kala-azar ...........................................................144 Keratoconjunctivitis, viral epidemic.............125 Kwashiorkor.......................................................40 Laboratory, examinations .................................11 Labour, premature ...........................................249 Laryngitis acute .................................................51 Leg ulcers..........................................................281 Leishmaniases ..................................................144 Leprosy..............................................................113 Leptospirosis ....................................................180
Leukoplakia, oral .............................................214 Lice.....................................................................101 Loiasis.........................................................128,159 Louse-borne relapsing fever ..........................182 Lower abdominal pain in women.................239 Lumbar puncture.............................................166 Lymphadenopathy, persistent generalised ...216 Lymphogranuloma venereum.......................236 Malaria ..............................................................131 Malnutrition .......................................................40 Marasmus ...........................................................40 Measles..............................................................189 Meningitis, bacterial........................................165 Meningitis, parasitic........................................218 Mental confusion .............................................294 Metrorrhagia ....................................................246 Microsporidium ..................................................213 Myositis of the psoas.......................................280 Necrotising infections of the skin..................108 Nematode infections .......................................154 Neurosyphilis...................................................218 Oedema, acute pulmonary.............................308 Onchocerciasis...........................................128,157 Opistorchiasis...................................................149 Otitis externa, acute...........................................57 Otitis media, acute.............................................57 Otitis media, chronic suppurative...................59 Pain evaluation scales .......................................30 Pain ......................................................................29 Pain, lower abdominal (in women) ..............239 Panic disorder ..................................................291 Papilloma viruses .....................................243,245 Paragonimiasis.................................................149 Paralysis, acute flaccid ....................................193 Pediculosis ........................................................101 Pellagra..............................................................118 Penicilliosis .......................................................215 Peptic ulcer diseases..........................................89 Perforation, gastric ............................................90 Persistent generalised lymphadenopathy .....216 Pertussis ..............................................................60 Pharyngitis, acute ..............................................53 Pinta ...................................................................112 Placenta praevia...............................................248 Plague................................................................178 Pneumocystosis ...............................................215 Pneumonia, acute ..............................................66 Poliomyelitis.....................................................192 Post-partum haemorrhage .............................250
331
N O P
K L
Index
Post-traumatic stress disorder .......................295 Pre-delirium tremens ......................................293 Pre-eclampsia ...................................................307 Premature labour .............................................249 Prostatitis, acute...............................................228 Protozoan infections, intestinal .....................147 Psoas, myositis .................................................280 Psoriasis and HIV ............................................217 Psychotic disorders .........................................300 Psychosis...........................................................300 Pterygium .........................................................128 Pulmonary oedema, acute..............................308 Pulmonary tuberculosis....................................79 Pyelonephritis, acute.......................................226 Pyodermitis ......................................................105 Pyomyositis ......................................................279 Rabies ................................................................194 Relapsing fever ................................................182 Relapsing fever, louse-borne..........................182 Relapsing fever, tick-borne.............................183 Rheumatic fever, acute....................................310 Rhinitis ................................................................49 Rhinopharyngitis...............................................49 Rickettsioses, eruptive ....................................185 Ringworm .........................................................103 River blindness .........................................128,157 Salpingitis .........................................................240 Scabies .................................................................98 Scarlet fever ........................................................93 Schistosomiases................................................150 Schizophrenia...................................................300 Scurvy..................................................................94 Seborrhoeic dermatitis ....................................217 Seizures ...............................................................23 Severe acute malnutrition ................................40 Shigellosis ......................................................83,86 Shingles .............................................................116 Shock ...................................................................17 Shock, anaphylactic...........................................17 Shock, cardiogenic.............................................17 Shock, haemorrhagic.........................................17 Shock, hypovolaemic ........................................17 Shock, septic .......................................................17 Sinusitis, acute....................................................50 Skin infections, bacterial.................................105 Skin, necrotising infections ............................108 Sleeping sickness .............................................139 Staphylococcal pneumonia .......................73,215 Stings, venomous.............................................283 Stomach disorders .............................................89 Stomatitis ............................................................92 Strongyloidiasis ...............................................155 Sutures...............................................................258 Syphillis......................................................236,245
332
Taeniasis ............................................................152 Tehmoiditis, acute..............................................50 Tetanus ..............................................................170 Threatened abortion ........................................247 Tick-borne relapsing fever..............................183 Toxoplasmosis, cerebral...........................218,219 Trachoma ..........................................................126 Transfusion, blood .............................................38 Tremonematoses...............................................111 Trichinellosis.....................................................156 Trichomoniasis ..........................................233,244 Trichuriasis .......................................................154 Trypanosomiasis, african................................139 Trypanosomiasis, american............................142 Tuberculosis, pulmonary ..................................79 Typhoid fever ...................................................174 Typhus...............................................................185 Ulcers, genital...................................................236 Ulcers, leg .........................................................281 Upper genital tract infections ........................240 Urethral discharge ...........................................231 Urolithiasis .......................................................223 Urticaria.............................................................117 Uterine rupture ................................................249 Vaginal discharge, abnormal..........................233 Vaginitis ............................................................233 Veneral warts.............................................243,245 Venoms..............................................................283 Violence, sexual.........................................230,322 Vitamin A deficiency .......................................121 Vitamin C deficiency .........................................94 Warts, veneral............................................243,245 Whooping cough ...............................................60 Wound, simple .................................................256 Xerophthalmia .................................................121 Xerosis, diffuse cutaneous..............................217 Yaws...................................................................112 Yellow fever ......................................................204
W X
Tuberculosis
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